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Levocarnitine

PubChem CID
10917
Structure
Levocarnitine_small.png
Levocarnitine_3D_Structure.png
Levocarnitine__Crystal_Structure.png
Molecular Formula
Synonyms
  • L-carnitine
  • Levocarnitine
  • 541-15-1
  • (R)-Carnitine
  • Carnitor
Molecular Weight
161.20 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-06-01
  • Modify:
    2025-01-18
Description
(R)-carnitine is the (R)-enantiomer of carnitine. It has a role as an antilipemic drug, a water-soluble vitamin (role), a nutraceutical, a nootropic agent and a Saccharomyces cerevisiae metabolite. It is a conjugate base of a (R)-carnitinium. It is an enantiomer of a (S)-carnitine.
Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias.
L-Carnitine is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Levocarnitine.png

1.2 3D Conformer

1.3 Crystal Structures

COD Number
Associated Article
Gandour, Richard David; Colucci, William Jay; Fronczek, Frank R.. Crystal structures of carnitine and acetylcarnitine zwitterions: A structural hypothesis for mode of action. Bioorganic Chemistry 1985;13(3):197-208. DOI: 10.1016/0045-2068(85)90022-7
Crystal Structure Depiction
Crystal Structure Depiction
Hermann-Mauguin space group symbol
P 1 21 1
Hall space group symbol
P 2yb
Space group number
4
a
7.342 Å
b
6.089 Å
c
9.530 Å
α
90 °
β
97.58 °
γ
90 °
Z
2
Z'
1

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(3R)-3-hydroxy-4-(trimethylazaniumyl)butanoate
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C7H15NO3/c1-8(2,3)5-6(9)4-7(10)11/h6,9H,4-5H2,1-3H3/t6-/m1/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

PHIQHXFUZVPYII-ZCFIWIBFSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C[N+](C)(C)C[C@@H](CC(=O)[O-])O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C7H15NO3
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

541-15-1

2.3.2 Deprecated CAS

7634-98-2

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 KEGG ID

2.3.10 Metabolomics Workbench ID

2.3.11 NCI Thesaurus Code

2.3.12 NSC Number

2.3.13 PharmGKB ID

2.3.14 RXCUI

2.3.15 Wikidata

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Bicarnesine
  • Carnitine
  • L Carnitine
  • L-Carnitine
  • Levocarnitine
  • Vitamin BT

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
161.20 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
-0.2
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
161.10519334 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
161.10519334 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
60.4 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
11
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
134
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
1
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Highly hygroscopic solid; [Merck Index] Crystalline solid; [Alfa Aesar MSDS]

3.2.2 Color / Form

White, crystalline, hygroscopic powder
Physicians Desk Reference. 59th ed. Thomson PDR. Montvale, NJ 2005., p. 3144

3.2.3 Melting Point

195-198
Noguchi, J. and Sakota, N.; US. Patent 3,135,788; June 2,1964; assigned to Nihon Zoki Seiyaku Kabushikikaisha (Japan).
197 °C (dec)
Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL 2005, p. 3-88

3.2.4 Solubility

2500 mg/mL
Readily soluble in water and hot alcohol. Practically insoluble in acetone, ether and benzene
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 300

3.2.5 Optical Rotation

The specific optical rotation is between -29 and -32
Physicians Desk Reference. 59th ed. Thomson PDR. Montvale, NJ 2005., p. 3144

3.2.6 Dissociation Constants

pKa
3.8

3.2.7 Collision Cross Section

132.9 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]
130 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine]
133.1 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]
132.9 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

3.3 Chemical Classes

Biological Agents -> Amino Acids and Derivatives

3.3.1 Drugs

Pharmaceuticals -> unsed in Switzerland 2014-2016
S113 | SWISSPHARMA24 | 2024 Swiss Pharmaceutical List with Metabolites | DOI:10.5281/zenodo.10501043
3.3.1.1 Human Drugs
Human drug -> Prescription
Human drug -> Prescription; Discontinued
Human drug -> Prescription; Discontinued; Active ingredient (LEVOCARNITINE)

3.3.2 Cosmetics

Cosmetic ingredients (Carnitine HCl) -> CIR (Cosmetic Ingredient Review)
Foam boosting; Cleansing
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

3.3.3 Food Additives

NUTRIENT SUPPLEMENT -> FDA Substance added to food

4 Spectral Information

4.1 1D NMR Spectra

4.1.1 1H NMR Spectra

Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
439584
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 13C NMR Spectra

1 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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2 of 2
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
439584
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 MS-MS

1 of 2
NIST Number
1006042
Instrument Type
IT/ion trap
Collision Energy
0
Spectrum Type
MS2
Precursor Type
[M+H]+
Precursor m/z
162.1125
Total Peaks
3
m/z Top Peak
103
m/z 2nd Highest
60
m/z 3rd Highest
102
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2 of 2
NIST Number
1054087
Instrument Type
IT/ion trap
Collision Energy
0
Spectrum Type
MS2
Precursor Type
[M+H]+
Precursor m/z
162.1125
Total Peaks
5
m/z Top Peak
103
m/z 2nd Highest
60
m/z 3rd Highest
102.1
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4.2.2 LC-MS

1 of 14
View All
Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6530 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
20 eV
Fragmentation Mode
CID
Retention Time
0.598 min
Precursor m/z
162.1125
Precursor Adduct
[M+H]+
Top 5 Peaks

60.0808 999

43.0184 963

103.0377 782

85.0279 766

102.0904 554

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License
CC BY
2 of 14
View All
Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6530 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
40 eV
Fragmentation Mode
CID
Retention Time
0.563 min
Precursor m/z
162.1125
Precursor Adduct
[M+H]+
Top 5 Peaks

58.0651 999

43.0181 892

60.0806 316

44.0497 257

45.0571 244

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License
CC BY

4.2.3 Other MS

1 of 10
View All
Authors
Atsushi Yamamoto, Faculty of Environmental Studies, Tottori University of Environmental Studies, 1-1, Wakabadai-kita, Tottori City, Tottori 689-1111, Japan.
Instrument
X500R QTOF (AB Sciex LLC, USA)
Instrument Type
ESI-QTOF
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ESI
Top 5 Peaks

184.0937 999

162.1118 897

125.0207 123

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License
CC BY
2 of 10
View All
Authors
Atsushi Yamamoto, Faculty of Environmental Studies, Tottori University of Environmental Studies, 1-1, Wakabadai-kita, Tottori City, Tottori 689-1111, Japan.
Instrument
X500R QTOF (AB Sciex LLC, USA)
Instrument Type
ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10 V
Fragmentation Mode
CID
Precursor m/z
162.11247
Precursor Adduct
[M+H]+
Top 5 Peaks
162.112 999
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License
CC BY

4.3 IR Spectra

4.3.1 FTIR Spectra

Instrument Name
Bruker Tensor 27 FT-IR
Technique
KBr1
Source of Spectrum
Bio-Rad Laboratories, Inc.
Source of Sample
Acros Organics
Catalog Number
241040010
Lot Number
A0366760
Copyright
Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.3.2 ATR-IR Spectra

1 of 2
Instrument Name
Bruker Tensor 27 FT-IR
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Bio-Rad Laboratories, Inc.
Source of Sample
Acros Organics
Catalog Number
241040010
Lot Number
A0366760
Copyright
Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Sample
Aldrich
Catalog Number
439584
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4 Raman Spectra

Instrument Name
Bruker MultiRAM Stand Alone FT-Raman Spectrometer
Technique
FT-Raman
Source of Spectrum
Bio-Rad Laboratories, Inc.
Source of Sample
Acros Organics
Catalog Number
241040010
Lot Number
A0366760
Copyright
Copyright © 2017-2024 John Wiley & Sons, Inc. All Rights Reserved.
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6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

For treatment of primary systemic carnitine deficiency, a genetic impairment of normal biosynthesis or utilization of levocarnitine from dietary sources, or for the treatment of secondary carnitine deficiency resulting from an inborn error of metabolism such as glutaric aciduria II, methyl malonic aciduria, propionic acidemia, and medium chain fatty acylCoA dehydrogenase deficiency. Used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. Parenteral levocarnitine is indicated for the prevention and treatment of carnitine deficiency in patients with end-stage renal disease.

7.2 FDA Approved Drugs

7.3 FDA Orange Book

7.4 FDA National Drug Code Directory

7.5 Drug Labels

Drug and label
Active ingredient and drug

7.6 Clinical Trials

7.6.1 ClinicalTrials.gov

7.6.2 EU Clinical Trials Register

7.6.3 NIPH Clinical Trials Search of Japan

7.7 Therapeutic Uses

Levocarnitine is indicated for treatment of primary systemic carnitine deficiency, a genetic impairment of normal biosynthesis or utilization of levocarnitine from dietary sources, or for the treatment of secondary carnitine deficiency resulting from an inborn error of metabolism. /Included in US product labeling/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1819
Parenteral levocarnitine is indicated for the prevention and treatment of carnitine deficiency in patients with end-stage renal disease supported on hemodialysis. /Included in US product labeling/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1819
Levocarnitine oral solution is used for the prevention and treatment of carnitine deficiency secondary to valproic acid toxicity. /NOT included in US product labeling/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1820
L-Carnitine, acetyl-L-carnitine, and/or propionyl-L-carnitine may be used for replacement therapy to restore normal carnitine concn and/or a normal nonesterified-to-esterified carnitine ratio ... For primary and some secondary carnitine deficiencies ... L-carnitine is used for replacement therapy.
Coates, P.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., White, J.D. (Ed), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, NY, p. 76 (2005)
For more Therapeutic Uses (Complete) data for L-CARNITINE (29 total), please visit the HSDB record page.

7.8 Drug Warnings

Various mild gastrointestinal complaints have been reported during the long-term administration of oral L- or D,L-carnitine; these include transient nausea and vomiting, abdominal cramps, and diarrhea. Mild myasthenia has been described only in uremic patients receiving D,L-carnitine. Gastrointestinal adverse reactions with carnitor (levocarnitine) Oral Solution or carnitor SF (levocarnitine) Sugar-Free Oral Solution dissolved in liquids might be avoided by a slow consumption of the solution or by a greater dilution. Decreasing the dosage often diminishes or eliminates drug-related patient body odor or gastrointestinal symptoms when present. Tolerance should be monitored very closely during the first week of administration, and after any dosage increases. Seizures have been reported to occur in patients with or without pre-existing seizure activity receiving either oral or intravenous levocarnitine. In patients with pre-existing seizure activity, an increase in seizure frequency and/or severity has been reported.
Physicians Desk Reference 61st ed, Thomson PDR, Montvale, NJ 2007., p. 3189
... Oral L-carnitine at a dose of 1 g daily was administered for twelve days to six patients with end-stage renal disease undergoing hemodialysis thrice weekly. Pre-dialysis plasma concentrations of L-carnitine (mean +/- SD) increased significantly (P < 0.05) from day 1 (baseline; 32.4 +/- 6.1 uM) to day 8 (66.1 +/- 13.8 uM) remaining constant thereafter. Although plasma levels of trimethylamine remained unaltered, the pre-dialysis plasma concentrations of trimethylamine-N-oxide increased significantly (P < 0.05) from day 1 (289.1 +/- 236.1 microM) to day 12 (529.0 +/- 237.9 uM). The hemodialysis clearances for L-carnitine, trimethylamine and trimethylamine-N-oxide were 14.3 +/- 8.2, 14.1 +/- 10.6 and 12.4 +/- 5.4 L/h, respectively, indicating their efficient removal by dialysis. Oral administration of L-carnitine at a dose of 1 g daily increases plasma concentrations of this substance to physiological levels in patients with end-stage renal disease who are undergoing hemodialysis. However, concerns about the possible deleterious consequences of such a dosage regimen still remain given that plasma concentrations of trimethylamine-N-oxide were continually rising and approximately doubled in a two-week period.
Bain MA et al; Curr Drug Metab 7 (7): 811-6 (2006)
... Patients with primary carnitine deficiency display alterations in the renal handling of L-carnitine and/or the transport of the compound into muscle tissue. Similarly, many forms of secondary carnitine deficiency, including some drug-induced disorders, arise from impaired renal tubular reabsorption. Patients with end-stage renal disease undergoing dialysis can develop a secondary carnitine deficiency due to the unrestricted loss of L-carnitine through the dialyser ...
Evans AM et al; Clin Pharmacokinet 42 (11): 941-67 (2003)
The aim of our work was to test the influence of L-carnitine supplementation on secondary hyperparathyroidism and bone metabolism in hemodialyzed patients in a randomized study. Eighty-three chronically hemodialyzed patients were observed; 44 were supplemented with L-carnitine (15 mg/kg iv after each hemodialysis for 6 months), while 39 took placebo. Levels of free carnitine (CAR), calcium (Ca), inorganic phosphate (P), Ca x P product, parathormone (PTH), bone-specific alkaline phosphatase (b-ALP), osteocalcin (OC), and osteoprotegerin (OPG) were monitored. In comparison with pretreatment values, changes of some selected parameters occurred in the supplemented patients after 6 months (data are expressed as medians; NS, nonsignificant change): PTH, 186.0 vs. 135.5 ng/L (NS); b-ALP, 13.9 vs. 13.2 ug/L (P < 0.05); OC, 78.3 vs. 68.8 ug/L (NS); OPG, 144.0 vs. 182.0 ng/L (P < 0.05). In the controls, there were the following changes: PTH, 148.0 vs. 207.0 ng/L (NS); b-ALP, 15.2 vs. 13.2 ug/L (P < 0.05); OC, 62.7 vs. 79.8 ug/L (P < 0.05); OPG, 140.0 vs. 164.0 ng/L (NS). A significant correlation was found between CAR and OPG changes (r = 0.51, P < 0.001) in the supplemented patients. The supplementation led to a significant increase of serum OPG concentration. Nevertheless, ...only nonsignificant tendencies to correction of secondary hyperparathyroidism and reduction of bone turnover in hemodialyzed patients supplemented with L-carnitine /were observed/ in contrast to controls. At this point, the use of L-carnitine does not seem to be justified.
Cibulka R et al; Calcif Tissue Int 81 (2): 99-106 (2007)
For more Drug Warnings (Complete) data for L-CARNITINE (9 total), please visit the HSDB record page.

7.9 Biomarker Information

8 Food Additives and Ingredients

8.1 FDA Substances Added to Food

Substance
Used for (Technical Effect)
NUTRIENT SUPPLEMENT

9 Pharmacology and Biochemistry

9.1 Pharmacodynamics

Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Lack of carnitine can lead to liver, heart, and muscle problems. Carnitine deficiency is defined biochemically as abnormally low plasma concentrations of free carnitine, less than 20 µmol/L at one week post term and may be associated with low tissue and/or urine concentrations. Further, this condition may be associated with a plasma concentration ratio of acylcarnitine/levocarnitine greater than 0.4 or abnormally elevated concentrations of acylcarnitine in the urine. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. The "vitamin BT" form actually contains D,L-carnitine, which competitively inhibits levocarnitine and can cause deficiency. Levocarnitine can be used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias.

9.2 FDA Pharmacological Classification

1 of 2
FDA UNII
0G389FZZ9M
Active Moiety
LEVOCARNITINE
Pharmacological Classes
Chemical Structure [CS] - Carnitine
Pharmacological Classes
Established Pharmacologic Class [EPC] - Carnitine Analog
FDA Pharmacology Summary
Levocarnitine is a Carnitine Analog.
2 of 2
Non-Proprietary Name
LEVOCARNITINE
Pharmacological Classes
Carnitine [CS]; Carnitine Analog [EPC]

9.3 ATC Code

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

A - Alimentary tract and metabolism

A16 - Other alimentary tract and metabolism products

A16A - Other alimentary tract and metabolism products

A16AA - Amino acids and derivatives

A16AA01 - Levocarnitine

9.4 Bionecessity

L-Carnitine participates in a reversible transesterification reaction, in which an acyl group is transferred from coenzyme A to the hydroxyl group of L-carnitine ... /This reaction facilitates the/ transfer of long-chain fatty acids from cytoplasm ... /and/ chain-shortened /very-long-chain/ fatty acids from peroxisomes to mitochondria /and the/ modulation of the acyl-CoA/CoA ratio in cellular compartments.
Coates, P.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., White, J.D. (Ed), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, NY, p. 73 (2005)
L-Carnitine and extramitochondrial carnitine palmitoyltransferase (CPT, /catalyzing transesterification between coenzyme A and L-carnitine/) are important modulators of long-chain fatty acid utilization for membrane phospholipid biosynthesis and remodeling. L-Carnitine acts as a reservoir of long-chain fatty acids for incorporation into erythrocyte membrane phospholipids during repair after oxidative insults, and for use in the synthesis of dipalmitoylphosphatidylcholine, the major component of surfactant, in lung alveolar cells.
Coates, P.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., White, J.D. (Ed), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, NY, p. 75 (2005)
Although L-carnitine is supplied exogenously as a component of the diet and can also be synthesized endogenously, evidence suggests both primary and secondary deficiencies do occur. Carnitine deficiency can be acquired or a result of inborn errors of metabolism. Pre-term infants are at risk for developing a carnitine deficiency due to impaired synthesis and insufficient renal tubular resorption. Deficiency can result in cardiomyopathy, congestive heart failure, encephalopathy, hepatomegaly, impaired growth and development in infants, and neuromuscular disorders. Primary carnitine deficiency, although rare, is characterized by low plasma, red blood cell, and tissue levels of carnitine, and generally presents with symptoms such as muscle fatigue, cramps, and myoglobinemia following exercise. Additional symptoms of chronic carnitine deficiency can include hypoglycemia, progressive myasthenia, hypotonia, or lethargy. Secondary carnitine deficiency is not as rare and is most commonly associated with dialysis in chronic renal failure, although it can also be induced by intestinal resection, severe infection, and liver disease. Other conditions associated with a carnitine deficiency include cancer, diabetes, Alzheimer's disease, and heart failure. Pathological manifestations of chronic deficiency include accumulation of neutral lipid within skeletal muscle, cardiac muscle, and liver; a disruption of muscle fibers; and an accumulation of large aggregates of mitochondria within skeletal and smooth muscle.
Thorne Research, Inc.; Monograph on L-Carnitine; Alternative Medicine Review 10(1) p.43 (2005). Available from, as of February 22, 2008: https://www.thorne.com/altmedrev/.fulltext/10/1/42.pdf
HIV-infected individuals often accumulate fat in some areas of the body and lose fat in others and develop high levels of blood fats (hyperlipidemia) and insulin resistance, which together constitute the lipodystrophy syndrome. This syndrome may represent mitochondrial toxicity brought about by the HIV infection and the antiretroviral drugs used to treat it, and can induce a carnitine deficiency that limits mitochondrial fat metabolism. /Carnitine/
NIH/ODS; Dietary Supplement Fact Sheets on Carnitine (6/15/2006). Available from, as of February 26, 2008: https://ods.od.nih.gov/factsheets/carnitine.asp
For more Bionecessity (Complete) data for L-CARNITINE (16 total), please visit the HSDB record page.

9.5 Absorption, Distribution and Excretion

Absorption
Absolute bioavailability is 15% (tablets or solution). Time to maximum plasma concentration was found to be 3.3 hours.
Route of Elimination
Following a single intravenous dose, 73.1 +/- 16% of the dose was excreted in the urine during the 0-24 hour interval. Post administration of oral carnitine supplements, in addition to a high carnitine diet, 58-65% of the administered radioactive dose was recovered from urine and feces in 5-11 days.
Volume of Distribution
The steady state volume of distribution (Vss) of an intravenously administered dose, above endogenous baseline levels, was calculated to be 29.0 +/- 7.1L. However this value is predicted to be an underestimate of the true Vss.
Clearance
Total body clearance was found to be a mean of 4L/h.
L-Carnitine is a naturally occurring compound that facilitates the transport of fatty acids into mitochondria for beta-oxidation. ... In humans, the endogenous carnitine pool, which comprises free L-carnitine and a range of short-, medium- and long-chain esters, is maintained by absorption of L-carnitine from dietary sources, biosynthesis within the body and extensive renal tubular reabsorption from glomerular filtrate. In addition, carrier-mediated transport ensures high tissue-to-plasma concentration ratios in tissues that depend critically on fatty acid oxidation. The absorption of L-carnitine after oral administration occurs partly via carrier-mediated transport and partly by passive diffusion. After oral doses of 1-6 g, the absolute bioavailability is 5-18%. In contrast, the bioavailability of dietary L-carnitine may be as high as 75%. Therefore, pharmacological or supplemental doses of L-carnitine are absorbed less efficiently than the relatively smaller amounts present within a normal diet. L-Carnitine and its short-chain esters do not bind to plasma proteins and, although blood cells contain L-carnitine, the rate of distribution between erythrocytes and plasma is extremely slow in whole blood. After iv administration, the initial distribution volume of L-carnitine is typically about 0.2-0.3 L/kg, which corresponds to extracellular fluid volume. There are at least three distinct pharmacokinetic compartments for L-carnitine, with the slowest equilibrating pool comprising skeletal and cardiac muscle. L-Carnitine is eliminated from the body mainly via urinary excretion. Under baseline conditions, the renal clearance of L-carnitine (1-3 mL/min) is substantially less than glomerular filtration rate (GFR), indicating extensive (98-99%) tubular reabsorption. The threshold concentration for tubular reabsorption (above which the fractional reabsorption begins to decline) is about 40-60 umol/L, which is similar to the endogenous plasma L-carnitine level. Therefore, the renal clearance of L-carnitine increases after exogenous administration, approaching GFR after high iv doses. ...
Evans AM et al; Clin Pharmacokinet 42 (11): 941-67 (2003)
In mammals, the carnitine pool consists of nonesterified L-carnitine and many acylcarnitine esters. Of these esters, acetyl-L-carnitine is quantitatively and functionally the most significant. Carnitine homeostasis is maintained by absorption from diet, a modest rate of synthesis, and efficient renal reabsorption. Dietary L-carnitine is absorbed by active and passive transfer across enterocyte membranes. Bioavailability of dietary L-carnitine is 54-87% and is dependent on the amount of L-carnitine in the meal. Absorption of L-carnitine dietary supplements (0.5-6 g) is primarily passive; bioavailability is 14-18% of dose. Unabsorbed L-carnitine is mostly degraded by microorganisms in the large intestine. Circulating L-carnitine is distributed to two kinetically defined compartments: one large and slow-turnover (presumably muscle), and another relatively small and rapid-turnover (presumably liver, kidney, and other tissues). At normal dietary L-carnitine intake, whole-body turnover time in humans is 38-119 hr. In vitro experiments suggest that acetyl-L-carnitine is partially hydrolyzed in enterocytes during absorption. In vivo, circulating acetyl-L-carnitine concentration was increased 43% after oral acetyl-L-carnitine supplements of 2 g/day, indicating that acetyl-L-carnitine is absorbed at least partially without hydrolysis. After single-dose intravenous administration (0.5 g), acetyl-L-carnitine is rapidly, but not completely hydrolyzed, and acetyl-L-carnitine and L-carnitine concentrations return to baseline within 12 h. At normal circulating l-carnitine concentrations, renal l-carnitine reabsorption is highly efficient (90-99% of filtered load; clearance, 1-3 mL/min), but displays saturation kinetics. Thus, as circulating L-carnitine concentration increases (as after high-dose intravenous or oral administration of L-carnitine), efficiency of reabsorption decreases and clearance increases, resulting in rapid decline of circulating L-carnitine concentration to baseline. Elimination kinetics for acetyl-L-carnitine are similar to those for L-carnitine. There is evidence for renal tubular secretion of both L-carnitine and acetyl-L-carnitine. ...
Rebouche CJ; Ann N Y Acad Sci 1033:30-41 (2004)
The pharmacokinetics of L-carnitine and its metabolites were investigated in 7 healthy subjects following the oral administration of 0, 0.5, 1, and 2 g 3 times a day for 7 days. Mean plasma concentrations of L-carnitine across an 8-hour dose interval increased significantly (P < 0.05) from a baseline of 54.2 +/- 9.3 uM to 80.5 +/- 12.5 uM following the 0.5-g dose; there was no further increase at higher doses. There was a significant increase (P <0.001) in the renal clearance of L-carnitine indicating saturation of tubular reabsorption. Trimethylamine plasma levels increased proportionately with L-carnitine dose, but there was no change in renal clearance. A significant increase in the plasma concentrations of trimethylamine-N-oxide from baseline was evident only for the 2-g dose of L-carnitine (from 34.5 +/- 2.0 to 149 +/- 145 uM), and its renal clearance decreased with increasing dose (P <0.05). There was no evidence for nonlinearity in the metabolism of trimethylamine to trimethylamine-N-oxide. In conclusion, the pharmacokinetics of oral L-carnitine display nonlinearity above a dose of 0.5 g 3 times a day.
Bain MA et al; J Clin Pharmacol 46 (10): 1163-70 (2006)
Evidence indicates L-carnitine is absorbed in the intestine by a combination of active transport and passive diffusion. Reports of bioavailability following an oral dose have varied substantially, with estimates as low as 16 to 18% and as high as 54 to 87% ... The mucosal absorption of carnitine appears to be saturated at about a 2-g dose. Max blood concn is reached approx 3.5 hr after an oral dose and slowly decr, with a half-life of about 15 hr. Elimination of carnitine occurs primarily through the kidneys. The heart, skeletal muscle, liver, kidneys, and epididymis have specific transport systems for carnitine that concentrate carnitine within these tissues. Despite evidence indicating incr levels of free carnitine and carnitine metabolites in the blood and urine following an oral dose, no significant change in RBC carnitine levels was noted in healthy subjects, suggesting either a slow repletion of tissue stores of carnitine following an oral dose or a low capability to transport carnitine into tissues under normal conditions.
Thorne Research, Inc.; Monograph on L-Carnitine; Alternative Medicine Review 10(1) p.42 (2005). Available from, as of February 22, 2008: https://www.thorne.com/altmedrev/.fulltext/10/1/42.pdf
For more Absorption, Distribution and Excretion (Complete) data for L-CARNITINE (11 total), please visit the HSDB record page.

9.6 Metabolism / Metabolites

After oral administration L-carnitine which is unabsorbed is metabolized in the gastrointestinal tract by bacterial microflora. Major metabolites include trimethylamine N-oxide and [3H]-gamma-butyrobetaine.
In mammals, L-carnitine is synthesized from epsilon-N-trimethyllysine, which is derived from post-translationally methylated lysine residues in proteins, and protein turnover. In normal humans, the rate of synth is est to be ca 1.2 umol/kg/day. The rate of L-carnitine biosynth is regulated by the avail of epsilon-N-trimethyllysine. Thus, conditions that incr protein methylation and/or protein turnover may incr the rate of L-carnitine biosynth.
Coates, P.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., White, J.D. (Ed), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, NY, p. 75 (2005)
Synthesis of carnitine begins with methylation of the amino acid L-lysine by S-adenosylmethionine (SAMe). Magnesium, vitamin C, iron, vitamins B3 and B6, and alpha-ketoglutarate - along with the cofactors responsible for creating SAMe (methionine, folic acid, vitamin B12, and betaine) - are all required for endogenous carnitine synthesis.
Thorne Research, Inc.; Monograph on L-Carnitine; Alternative Medicine Review 10(1) p.42 (2005). Available from, as of February 22, 2008: https://www.thorne.com/altmedrev/.fulltext/10/1/42.pdf
Unabsorbed L-carnitine is degraded by micro-organisms in the large intestine. Major metabolites identified are trimethylamine oxide in urine and gamma-butyrobetaine in feces.
Coates, P.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., White, J.D. (Ed), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, NY, p. 75 (2005)
Carnitine plays an indispensable role in fatty acid oxidation. Previous studies revealed that fetal carnitine is derived from the mother via transplacental transfer. Recent studies demonstrated the presence and importance of an active fatty acid oxidation system in the human placenta and in the human fetus. In view of these findings ... carnitine metabolism /was studied/ in the fetal-placental unit by measuring carnitine metabolites, intermediary metabolites of carnitine biosynthesis, as well as the activity of carnitine biosynthesis enzymes in human term placenta, cord blood and selected embryonic and fetal tissues (5-20 weeks of development). Placenta contained low but detectable activity of gamma-butyrobetaine dioxygenase. This enzyme, which was considered to be expressed only in kidney, liver and brain, catalyzes the last step in the carnitine biosynthesis pathway. In addition, ... human fetal kidney, liver and spinal cord already have the capacity to synthesize carnitine. The ability of the placenta and fetus to synthesize carnitine suggests that in circumstances when maternal carnitine supply is limited, carnitine biosynthesis by the fetal-placental unit may supply sufficient carnitine for placental and fetal metabolism. /Carnitine/
Oey NA et al; Placenta 27 (8): 841-6 (2006)
For more Metabolism/Metabolites (Complete) data for L-CARNITINE (7 total), please visit the HSDB record page.
After oral administration L-carnitine which is unabsorbed is metabolized in the gastrointestinal tract by bacterial microflora. Major metabolites include trimethylamine N-oxide and [3H]-gamma-butyrobetaine. Route of Elimination: Following a single intravenous dose, 73.1 +/- 16% of the dose was excreted in the urine during the 0-24 hour interval. Post administration of oral carnitine supplements, in addition to a high carnitine diet, 58-65% of the administered radioactive dose was recovered from urine and feces in 5-11 days. Half Life: 17.4 hours (elimination) following a single intravenous dose.

9.7 Biological Half-Life

17.4 hours (elimination) following a single intravenous dose.
Distribution: 0.585 hours; Elimination: 17.4 hours
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1820
... Half-life /in blood/ ca 15 hr ...
Thorne Research, Inc.; Monograph on L-Carnitine; Alternative Medicine Review 10(1) p.42 (2005). Available from, as of February 22, 2008: https://www.thorne.com/altmedrev/.fulltext/10/1/42.pdf

9.8 Mechanism of Action

Levocarnitine can be synthesised within the body from the amino acids lysine or methionine. Vitamin C (ascorbic acid) is essential to the synthesis of carnitine. Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. Levocarnitine is handled by several proteins in different pathways including carnitine transporters, carnitine translocases, carnitine acetyltransferases and carnitine palmitoyltransferases.
L-Carnitine is a peripheral antagonist of thyroid hormone action in some tissues. It inhibits thyroid hormone entry into cell nuclei. In a controlled clinical trial, L-carnitine was shown to reverse or prevent some symptoms of hyperthyroidism.
Coates, P.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., White, J.D. (Ed), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, NY, p. 75 (2005)
... Mortality and metabolic consequences of acute ammonium intoxication in mice are reduced by pharmacologic admin of L-carnitine. The mechanism for this effect may have 2 components. L-Carnitine admin normalizes the redox state of the brain (perhaps by incr the avail of beta-hydroxybutyrate and/or acetyl-L-carnitine to the brain), and it incr the rate of urea synth in the liver, perhaps in part by activation of the glucocorticoid receptor. At least part of the protective effect is associated with flux through the carnitine acyltransferases, as analogs of L-carnitine that are competitive inhibitors of carnitine acyltransferases enhance the toxicity of acute ammonium admin. Thus, it has been proposed that L-carnitine incr urea synth in the liver by facilitating fatty acid entry into mitochondria, leading to incr flux through the beta-oxidation pathway, an incr of intramitochondrial reducing equivalents, and enhancement of ATP production. ...
Coates, P.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., White, J.D. (Ed), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, NY, p. 78 (2005)
Levocarnitine is necessary for normal mammalian fat utilization and energy metabolism. It facilitates entry of long-chain fatty acids into cellular mitochondria, where they are used during oxidation and energy production. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1820
Carnitine's primary mechanism of action is apparently attributable to its role as a cofactor in the transformation of free long-chain fatty acids into acylcarnitines for subsequent transport into the mitochondrial matrix. Carnitine is involved in the metabolism of ketones for energy and the conversion of branched-chain amino acids - valine, leucine, and isoleucine - into energy. /Carnitine/
Thorne Research, Inc.; Monograph on L-Carnitine; Alternative Medicine Review 10(1) p.43 (2005). Available from, as of February 22, 2008: https://www.thorne.com/altmedrev/.fulltext/10/1/42.pdf
L-Carnitine participates in a reversible transesterification reaction, in which an acyl group is transferred from coenzyme A to the hydroxyl group of L-carnitine ... /This reaction facilitates the/ transfer of long-chain fatty acids from cytoplasm ... /and/ chain-shortened /very-long-chain/ fatty acids from peroxisomes to mitochondria /and the/ modulation of the acyl-CoA/CoA ratio in cellular compartments.
Coates, P.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., White, J.D. (Ed), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, NY, p. 73 (2005)

9.9 Biochemical Reactions

10 Use and Manufacturing

10.1 Uses

Cosmetic Ingredient Review Link
CIR ingredient: Carnitine HCl
EPA CPDat Chemical and Product Categories
The Chemical and Products Database, a resource for exposure-relevant data on chemicals in consumer products, Scientific Data, volume 5, Article number: 180125 (2018), DOI:10.1038/sdata.2018.125
Sources/Uses
An essential cofactor in fatty acid metabolism; Highest concentrations in red meat, dairy, beans, and avocado; Used as a vitamin; [Merck Index]
Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013.
Used to treat carnitine deficiency
Physicians Desk Reference. 59th ed. Thomson PDR. Montvale, NJ 2005., p. 3144
Used therapeutically for myocardial injury after ischemia and reperfusion by counteracting the toxic effect of high levels of free fatty acids, which occur in ischemia, and by improving carbohydrate metabolism
Ferrari R et al; Ann NY Acad Sci 1033: 79-91 (2004)

Use (kg; approx.) in Germany (2009): >1000

Consumption (g per capita; approx.) in Germany (2009): 0.0122

Excretion rate: 0.09

Calculated removal (%): 92.1

For treatment of primary systemic carnitine deficiency, a genetic impairment of normal biosynthesis or utilization of levocarnitine from dietary sources, or for the treatment of secondary carnitine deficiency resulting from an inborn error of metabolism such as glutaric aciduria II, methyl malonic aciduria, propionic acidemia, and medium chain fatty acylCoA dehydrogenase deficiency. Used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. Parenteral levocarnitine is indicated for the prevention and treatment of carnitine deficiency in patients with end-stage renal disease.

10.1.1 Use Classification

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Cosmetics -> Foam boosting; Cleansing
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

10.2 Methods of Manufacturing

Enantioselective synthesis from glycerol
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 300

10.3 Formulations / Preparations

Levocarnitine oral solution USP: 100 mg/mL (Carnitor). Levocarnitine tablets USP: 330 mg (Carnitor). Levocarnitine injection: 200 mg/mL (Carnitor).
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1822
L-carnitine is avail in a few forms: oral L-carnitine ... iv L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine. The avail salts ... are L-carnitine HCL, L-carnitine tartrate and L-carnitine fumarate ... /Supplied in/ capsules, injection, liquid, solution, tablets, wafer
Thomson Healthcare. PDR for Nutritional Supplements. Thomson Health Care Inc. Montvale, NJ. p.258 (2001)
Trade names: Carnitor ... Carnitine-300 ... Carni Fuel ... Mega L-Carnitine ... Maximal Burner Carnitine ... Proxeed ...
Thomson Healthcare. PDR for Nutritional Supplements. Thomson Health Care Inc. Montvale, NJ. p.255 (2001)

11 Identification

11.1 Analytic Laboratory Methods

Analyte: levocarnitine; matrix: bulk material; procedure: high-performance liquid chromatography with fluorescence detection at 485 nm (excitation) and 540 nm (emission); limit of detection: 100 fmole
Matsumoto K et al; J Chromatogr A 678: 241-247 (1994). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CD-ROM. New York, NY: John Wiley & Sons (2000)
Analyte: levocarnitine; matrix: pharmaceutical preparation (tablet); procedure: high-performance liquid chromatography with fluorescence detection at 365 nm (excitation) and 412 nm (emission) or ultraviolet detection at 250 nm; limit of detection: 1 pg
Yoshida T et al; J Chromatogr 445: 175-182 (1988). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CD-ROM. New York, NY: John Wiley & Sons (2000)
Analyte: levocarnitine; matrix: pharmaceutical preparation (tablet); procedure: high-performance liquid chromatography with fluorescence detection at 355 nm (excitation) and 420 nm (emission); limit of detection: 500 ng/mL
Kamata K et al; J Chromatogr A 667: 113-118 (1994). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CD-ROM. New York, NY: John Wiley & Sons (2000)
Analyte: levocarnitine; matrix: pharmaceutical preparation (injection solution, syrup, tablet); procedure: high-performance liquid chromatography with ultraviolet detection at 254 nm; limit of detection: 50 ug/mL
Takahashi M et al; J Pharm Biomed Anal 14: 1579-1584 (1996). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CD-ROM. New York, NY: John Wiley & Sons (2000)
For more Analytic Laboratory Methods (Complete) data for L-CARNITINE (6 total), please visit the HSDB record page.

11.2 Clinical Laboratory Methods

Analyte: levocarnitine; matrix: blood (plasma); procedure: capillary electrophoresis with ultraviolet detection at 214 nm; limit of detection: 20 uM
Vogt C, Kiessig S; J Chromatogr A 745: 53-60 (1996). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CD-ROM. New York, NY: John Wiley & Sons (2000)
Analyte: levocarnitine; matrix: blood (plasma); procedure: capillary electrophoresis with fluorescence detection at 320 nm (excitation) and 405 nm (emission); limit of detection: <1 uM
Kiessig S, Vogt C; J Chromatogr A 781: 475-470 (1997). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CD-ROM. New York, NY: John Wiley & Sons (2000)
Analyte: levocarnitine; matrix: blood (plasma); procedure: high-performance liquid chromatography with fluorescence detection at 340 nm (excitation) and 475 nm (emission); limit of detection: 240 nM
Kuroda N et al; Chem Pharm Bull 44: 1525-1529 (1996). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CD-ROM. New York, NY: John Wiley & Sons (2000)
Analyte: levocarnitine; matrix: blood (plasma); procedure: high-performance liquid chromatography with fluorescence detection at 248 nm (excitation) and 418 nm (emission); limit of detection: 5 uM
Longo A et al; J Chromatogr B 686: 129-139 (1996). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CD-ROM. New York, NY: John Wiley & Sons (2000)
For more Clinical Laboratory Methods (Complete) data for L-CARNITINE (11 total), please visit the HSDB record page.

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

Note
Pictograms displayed are for 90.5% (1351 of 1493) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for 9.5% (142 of 1493) of reports.
Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H315 (90.5%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (90.5%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

Precautionary Statement Codes

P264, P264+P265, P280, P302+P352, P305+P351+P338, P321, P332+P317, P337+P317, and P362+P364

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 1493 reports by companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 142 of 1493 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 13 notifications provided by 1351 of 1493 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

12.1.2 Hazard Classes and Categories

Skin Irrit. 2 (90.5%)

Eye Irrit. 2 (90.5%)

12.1.3 Hazards Summary

May cause irritation; [Alfa Aesar MSDS]

12.2 Accidental Release Measures

12.2.1 Disposal Methods

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

12.3 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: 1-Propanaminium, 3-carboxy-2-hydroxy-N,N,N-trimethyl-, inner salt, (2R)-
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Carnitine: Does not have an individual approval but may be used under an appropriate group standard

12.3.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl levocarnitine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 24, 2008: https://www.fda.gov/cder/ob/
Since 1994, dietary supplements have been regulated under the Dietary Supplement Health and Education Act (DSHEA). The DSHEA requires no proof of safety for dietary supplements on the market prior to October 15, 1994. Labeling requirements for such supplements allow warnings and dosage recommendations as well as substantiated "structure or function" claims. All claims must prominently note that they have not been evaluated by the FDA, and they must bear the statement "This product is not intended to diagnose, treat, cure, or prevent any disease".
Croom EM, Walker L; Drug Topics (November 6): 84-93 (1995)

12.4 Other Safety Information

Chemical Assessment
Evaluation - Chemicals that are unlikely to require further regulation to manage risks to environment

12.4.1 Special Reports

Thorne Research, Inc.; Monograph on L-Carnitine; Alternative Medicine Review 10(1) (2005). Available from: http://www.thorne.com/altmedrev/.fulltext/10/1/42.pdf as of February 25, 2008.

13 Toxicity

13.1 Toxicological Information

13.1.1 Toxicity Summary

Levocarnitine can be synthesised within the body from the amino acids lysine or methionine. Vitamin C (ascorbic acid) is essential to the synthesis of carnitine. Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. Levocarnitine is handled by several proteins in different pathways including carnitine transporters, carnitine translocases, carnitine acetyltransferases and carnitine palmitoyltransferases.

13.1.2 Drug Induced Liver Injury

Compound
l-carnitine
DILI Annotation
No-DILI-Concern
Label Section
No match
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

13.1.3 Carcinogen Classification

Carcinogen Classification
No indication of carcinogenicity to humans (not listed by IARC).

13.1.4 Exposure Routes

Intravenous, Oral. Absolute bioavailability is 15% (tablets or solution). Time to maximum plasma concentration was found to be 3.3 hours.

13.1.5 Symptoms

Adverse effects include hypertension, fever, tachycardia and seizures.

13.1.6 Acute Effects

13.1.7 Toxicity Data

LD<sub>50</sub> > 8g/kg (mouse, oral).

13.1.8 Interactions

... The present study aimed to investigate whether an increase in whole body carnitine retention can be achieved through L-carnitine feeding in conjunction with a dietary-induced elevation in circulating insulin. On two randomized visits (study A), eight men ingested 3 g/day L-carnitine followed by 4 x 500-mL solutions, each containing flavored water (Con) or 94 g simple sugars (glucose syrup; CHO). In addition, 14 men ingested 3 g/day L-carnitine followed by 2 x 500 mL of either Con or CHO for 2 wk (study B). Carbohydrate ingestion in study A resulted in a fourfold greater serum insulin area under the curve when compared with Con (P < 0.001) and in a lower plasma TC concentration throughout the CHO visit (P < 0.05). Twenty-four-hour urinary TC excretion in the CHO visit was lower than in the Con visit in study A (155.0 +/- 10.7 vs. 212.1 +/- 17.2 mg; P < 0.05). In study B, daily urinary TC excretion increased after 3 days (65.9 +/- 18.0 to 281.0 +/- 35.0 mg; P < 0.001) and remained elevated throughout the Con trial. During the CHO trial, daily urinary TC excretion increased from a similar basal value of 53.8 +/- 9.2 to 166.8 +/- 17.3 mg after 3 days (P < 0.01), which was less than during the Con trial (P < 0.01), and it remained lower over the course of the study (P < 0.001). The difference in plasma TC concentration in study A and 24-h urinary TC excretion in both studies suggests that insulin augmented the retention of carnitine in the CHO trials.
Stephens FB et al; J Appl Physiol 102 (3): 1065-70 (2007)
... The effect of the anti-cancer drug carboplatin on plasma concentrations and urinary excretion of L-carnitine (LC) and its main ester, acetyl-L-carnitine (ALC), in cancer patients /was examined/. ... Treatment with carboplatin was associated with a marked urinary loss of LC and ALC, most likely due to inhibition of carnitine reabsorption in the kidney.
Mancinelli A et al; Cancer Chemother Pharmacol 60 (1): 19-26 (2007)
... The rats were divided into four groups: group 1, control (0.9% NaCl); group 2, doxorubicin (DOX) injection (7.5 mg/kg, i.v.); group 3, DOX plus low dose (40 mg/kg) L-carnitine; and group 4, DOX plus high dose (200 mg/kg) L-carnitine. L-carnitine was administered 1 h before doxorubicin injection and daily thereafter for 15 days. ... Rats in group 2 were associated with hypoalbuminemia, hyperlipidemia, high urinary excretion of protein and elevated plasma creatinine and urea nitrogen. The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) decreased with increased renal vascular resistance (RVR). Kidney catalase (CAT) activity was decreased. In group 3 and 4, plasma triglyceride and cholesterol declined. L-carnitine improved renal functions by elevated GFR and ERPF and decreased plasma creatinine and urea nitrogen. The kidney CAT activity were increased significantly compared with group 2. From histopathological results, group 2 rats were found to have glomerular capillary dilation and tubular dilation. The lesions were less in group 3 and 4 rats...
Boonsanit D et al' Nephrology (Carlton) 11 (4): 313-20 (2006). Comment in: Nephrology (Carlton) 11 (6): 569 (2006)
... Recent literature documents no cases of allergic reactions or serious side effects associated with the administration of carnitine when given patients with acute ingestions of valproic acid. Other findings suggest that carnitine increases the survival rate of patients who develop valproic-acid-induced hepatotoxicity. Early intervention with iv rather than enteral L-carnitine was associated with the greatest hepatic survival. Isolated pediatric case reports show that carnitine administration may reverse toxic metabolic pathways but may not hasten clinical improvement. .../Carnitine/
Russell S; Curr Opin Pediatr 19 (2): 206-10 (2007)
For more Interactions (Complete) data for L-CARNITINE (17 total), please visit the HSDB record page.

13.1.9 Antidote and Emergency Treatment

Treatment of overdose: To enhance elimination: Removing levocarnitine from plasma via hemodialysis. Supportive care: Treatment is symptomatic and supportive.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1821
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160-1

13.1.10 Human Toxicity Excerpts

/SIGNS AND SYMPTOMS/ At doses of approximately 3 grams/day, carnitine supplements may cause nausea, vomiting, abdominal cramps, diarrhea, and a "fishy" body odor. More rare side effects include muscle weakness in uremic patients and seizures in those with seizure disorders. /Carnitine/
NIH/ODS; Dietary Supplement Fact Sheets on Carnitine (6/15/2006). Available from, as of February 26, 2008: https://ods.od.nih.gov/factsheets/carnitine.asp
/SIGNS AND SYMPTOMS/ Mild myasthenia has been reported in uremic patients taking the racemic mixture D,L-carnitine. /D,L-carnitine/
Thomson Healthcare. PDR for Nutritional Supplements. Thomson Health Care Inc. Montvale, NJ. p.258 (2001)
/ALTERNATIVE and IN VITRO TESTS/ In Hela cells, L-carnitine reduced glucocorticoid receptor-alpha affinity for its steroid ligand, and triggered nuclear translocation of the receptor. It suppressed glucocorticoid receptor-mediated tumor necrosis factor-alpha and interleukin-12 release by human primary monocytes stimulated with lipopolysaccharide ex vivo. All the these effects of L-carnitine were concentration dependent.
Coates, P.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., White, J.D. (Ed), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, NY, p. 75 (2005)
/ALTERNATIVE and IN VITRO TESTS/ ... Whether addition of L-carnitine altered the tumor cytotoxic effects of epirubicin /was determined/ using a number of in vitro cell viability assays in different breast cancer cell lines including BT549, MDA-MB-435, NCI-ADR-RES, MCF7 and T47D. Additionally ... the ability of cells to respond to L-carnitine following analysis of the expression of carnitine metabolic enzymes by RT-PCR /was investigated/. ... Supplementation with L-carnitine had no effect on the ability of epirubicin to kill a variety of breast cancer cell lines. Additionally, no differences in the induction of apoptosis by epirubicin were observed. Furthermore, all cell lines examined expressed proteins required for carnitine uptake and use. ... These results suggest that supplementation with L-carnitine in patients undergoing epirubicin treatment could be safely used to reduce associated cardiotoxicities without fear that the efficacy of chemotherapy is jeopardized.
Delaney CE et al; Cancer Lett 252 (2): 195-207 (2007)
For more Human Toxicity Excerpts (Complete) data for L-CARNITINE (6 total), please visit the HSDB record page.

13.1.11 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... Normotensive, Wistar-Kyoto rats.... (n = 20) were orally administered 0.2 g carnitine/kg body weight per day for a total period of 8 weeks. Kinetic parameters of L-carnitine uptake were calculated by non-linear regression, and the relative abundance of the carnitine transporter, OCTN2, was determined by Western blot analysis. ... Initial rates and maximal overshoot levels of Na+-dependent L-carnitine transport were significantly reduced in BBMVs from L-carnitine-treated rats compared with untreated animals. Similarly, the maximal transport rate (Vmax) of OCTN2 was lower in treated rats. However, no differences were observed in the Michaelis constant (Km) or the diffusion constant (Kd) between the two groups of animals. The amount of OCTN2 protein was also decreased in L-carnitine-fed rats, this reduction being similar to that of the Vmax. These results were accompanied by an increase in the serum levels and also in the renal excretion of both free and esterified carnitine in treated rats, indicating that the long-term administration of L-carnitine leads to increased renal carnitine clearance. ... These findings suggest a downregulation of OCTN2 at the renal level, in the presence of high levels of carnitine.
Gomez-Amores L et al; Pharm Res 20 (8): 1133-40 (2003)
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproductive studies have been performed in rats and rabbits at doses up to 3.8 times the human doses used for the treatment of primary and secondary L-carnitine deficiency on the basis of surface area and have revealed no evidence of impaired fertility or harm to the fetus due to L-carnitine.
Thomson Healthcare. PDR for Nutritional Supplements. Thomson Health Care Inc. Montvale, NJ. p.257 (2001)
/ALTERNATIVE and IN VITRO TESTS/ ... Calf lens tissue was incubated with both L-carnitine and acetyl-L-cartinine (ALC) for 15 days. The results showed that while L-carnitine had no effect on in vitro glycation, acetyl-L-carnitine decreased crystallin glycation by 42 percent.
Thorne Research, Inc.; Monograph on Acetyl-L-Carnitine; Alternative Medicine Review 4(6) p.439 (1999). Available from, as of February 26, 2008: https://www.thorne.com/altmedrev/.fulltext/4/6/438.pdf
/GENOTOXICITY/ Mutagenicity data indicate no mutagenicity ...
Thorne Research, Inc.; Monograph on L-Carnitine; Alternative Medicine Review 10(1) p.47 (2005). Available from, as of February 25, 2008: https://www.thorne.com/altmedrev/.fulltext/10/1/42.pdf

13.1.12 Non-Human Toxicity Values

LD50 Rat iv 5.4 g/kg
Physicians Desk Reference 61st ed, Thomson PDR, Montvale, NJ 2007., p. 3190
LD50 Mouse oral 19.2 g/kg
Thomson Healthcare. PDR for Nutritional Supplements. Thomson Health Care Inc. Montvale, NJ. p.258 (2001)

13.1.13 Populations at Special Risk

Precautions: ... There are no adequate and well-controlled studies in pregnant women ... Supplemental L-carnitine should be used by pregnant women only if clearly indicated and only under medical supervision. It is not known whether L-carnitine is excreted in human milk. Supplemental L-carnitine is not advised for nursing mothers.Those with seizure disorders should only used L-carnitine under medical advisement and supervision.
Thomson Healthcare. PDR for Nutritional Supplements. Thomson Health Care Inc. Montvale, NJ. p.258 (2001)

13.1.14 Protein Binding

None

13.2 Ecological Information

13.2.1 Natural Pollution Sources

L-Carnitine is a naturally occurring compound that facilitates the transport of fatty acids into mitochondria for beta-oxidation. ... In humans, the endogenous carnitine pool, which comprises free L-carnitine and a range of short-, medium- and long-chain esters, is maintained by absorption of L-carnitine from dietary sources, biosynthesis within the body and extensive renal tubular reabsorption from glomerular filtrate.
Evans AM et al; Clin Pharmacokinet 42 (11): 941-67 (2003)

13.2.2 Environmental Water Concentrations

While data specific to L-carnitine were not located(SRC, 2008), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils into aquifers(1).
(1) Heberer T; Tox Lett 131: 5-17 (2002)
(2) Koplin DW et al; Environ Sci Toxicol 36: 1202-211 (2002)

14 Associated Disorders and Diseases

15 Literature

15.1 Consolidated References

15.2 NLM Curated PubMed Citations

15.3 Springer Nature References

15.4 Thieme References

15.5 Chemical Co-Occurrences in Literature

15.6 Chemical-Gene Co-Occurrences in Literature

15.7 Chemical-Disease Co-Occurrences in Literature

16 Patents

16.1 Depositor-Supplied Patent Identifiers

16.2 WIPO PATENTSCOPE

16.3 Chemical Co-Occurrences in Patents

16.4 Chemical-Disease Co-Occurrences in Patents

16.5 Chemical-Gene Co-Occurrences in Patents

17 Interactions and Pathways

17.1 Chemical-Target Interactions

17.2 Drug-Drug Interactions

17.3 Drug-Food Interactions

Take with food. Taking levocarnitine oral solution with meals may reduce gastrointestinal upset such as nausea, vomiting, and cramping.

17.4 Pathways

18 Biological Test Results

18.1 BioAssay Results

19 Taxonomy

WormJam Metabolites Local CSV for MetFrag | DOI:10.5281/zenodo.3403364
WormJam: A consensus C. elegans Metabolic Reconstruction and Metabolomics Community and Workshop Series, Worm, 6:2, e1373939, DOI:10.1080/21624054.2017.1373939
The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106
A metabolome atlas of the aging mouse brain. Nat Commun. 2021 Oct 15;12(1):6021. DOI:10.1038/s41467-021-26310-y. PMID:34654818; PMCID:PMC8519999.
The Metabolome Atlas of the Aging Mouse Brain: https://mouse.atlas.metabolomics.us

20 Classification

20.1 MeSH Tree

20.2 NCI Thesaurus Tree

20.3 ChEBI Ontology

20.4 KEGG: Drug

20.5 KEGG: ATC

20.6 KEGG: Risk Category of Japanese OTC Drugs

20.7 WHO ATC Classification System

20.8 FDA Pharm Classes

20.9 ChemIDplus

20.10 ChEMBL Target Tree

20.11 UN GHS Classification

20.12 EPA CPDat Classification

20.13 NORMAN Suspect List Exchange Classification

20.14 CCSBase Classification

20.15 EPA DSSTox Classification

20.16 LOTUS Tree

20.17 FDA Drug Type and Pharmacologic Classification

20.18 EPA Substance Registry Services Tree

20.19 MolGenie Organic Chemistry Ontology

21 Information Sources

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    1-Propanaminium, 3-carboxy-2-hydroxy-N,N,N-trimethyl-, inner salt, (2R)-
    https://services.industrialchemicals.gov.au/search-assessments/
    1-Propanaminium, 3-carboxy-2-hydroxy-N,N,N-trimethyl-, inner salt, (2R)-
    https://services.industrialchemicals.gov.au/search-inventory/
  2. CAS Common Chemistry
    LICENSE
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    https://creativecommons.org/licenses/by-nc/4.0/
  3. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  4. DrugBank
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    https://www.drugbank.ca/legal/terms_of_use
  5. DTP/NCI
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    https://www.cancer.gov/policies/copyright-reuse
  6. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  7. European Chemicals Agency (ECHA)
    LICENSE
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    https://echa.europa.eu/web/guest/legal-notice
    (R)-(3-carboxy-2-hydroxypropyl)trimethylammonium hydroxide
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  9. Hazardous Substances Data Bank (HSDB)
  10. New Zealand Environmental Protection Authority (EPA)
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    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
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    CCSbase Classification
    https://ccsbase.net/
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    LICENSE
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    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  15. LOTUS - the natural products occurrence database
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    https://lotus.nprod.net/
  16. NCI Thesaurus (NCIt)
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    https://www.cancer.gov/policies/copyright-reuse
  17. Open Targets
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    https://platform-docs.opentargets.org/licence
  18. Toxin and Toxin Target Database (T3DB)
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    http://www.t3db.ca/downloads
  19. Yeast Metabolome Database (YMDB)
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    http://www.ebi.ac.uk/Information/termsofuse.html
  21. ClinicalTrials.gov
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  22. Comparative Toxicogenomics Database (CTD)
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    http://ctdbase.org/about/legal.jsp
  23. Therapeutic Target Database (TTD)
  24. Cosmetic Ingredient Review (CIR)
  25. EPA Chemical and Products Database (CPDat)
  26. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
    LICENSE
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    https://haz-map.com/About
  27. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
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    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  28. Crystallography Open Database (COD)
    LICENSE
    All data in the COD and the database itself are dedicated to the public domain and licensed under the CC0 License. Users of the data should acknowledge the original authors of the structural data.
    https://creativecommons.org/publicdomain/zero/1.0/
  29. DailyMed
  30. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  31. Drugs@FDA
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  32. ECI Group, LCSB, University of Luxembourg
    LICENSE
    Data: CC-BY 4.0; Code: Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
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  33. KNApSAcK Species-Metabolite Database
  34. Natural Product Activity and Species Source (NPASS)
  35. West Coast Metabolomics Center-UC Davis
    Carnitine
  36. EU Clinical Trials Register
  37. FDA Orange Book
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  38. National Drug Code (NDC) Directory
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  39. FDA Substances Added to Food
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  40. KEGG
    LICENSE
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    https://www.kegg.jp/kegg/legal.html
    Therapeutic category of drugs in Japan
    http://www.genome.jp/kegg-bin/get_htext?br08301.keg
    Anatomical Therapeutic Chemical (ATC) classification
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    Risk category of Japanese OTC drugs
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    https://mona.fiehnlab.ucdavis.edu/documentation/license
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  45. NIPH Clinical Trials Search of Japan
  46. NIST Mass Spectrometry Data Center
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    https://www.nist.gov/srd/public-law
  47. NLM RxNorm Terminology
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  48. WHO Anatomical Therapeutic Chemical (ATC) Classification
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    https://www.whocc.no/copyright_disclaimer/
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  50. Rhea - Annotated Reactions Database
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    https://www.rhea-db.org/help/license-disclaimer
  51. SpectraBase
  52. Springer Nature
  53. Thieme Chemistry
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  54. Wikidata
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    https://www.nlm.nih.gov/copyright.html
  56. PubChem
  57. GHS Classification (UNECE)
  58. EPA Substance Registry Services
  59. MolGenie
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  60. PATENTSCOPE (WIPO)
  61. NCBI
CONTENTS