An official website of the United States government

Oseltamivir

PubChem CID
65028
Structure
Oseltamivir_small.png
Oseltamivir_3D_Structure.png
Molecular Formula
Synonyms
  • oseltamivir
  • 196618-13-0
  • Tamvir
  • (-)-oseltamivir
  • Tamiflu-Free
Molecular Weight
312.40 g/mol
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Dates
  • Create:
    2005-06-24
  • Modify:
    2025-01-18
Description
Oseltamivir is a cyclohexenecarboxylate ester that is the ethyl ester of oseltamivir acid. An antiviral prodrug (it is hydrolysed to the active free carboxylic acid in the liver), it is used to slow the spread of influenza. It has a role as a prodrug, an EC 3.2.1.18 (exo-alpha-sialidase) inhibitor, an antiviral drug, an environmental contaminant and a xenobiotic. It is a cyclohexenecarboxylate ester, an amino acid ester, a primary amino compound and a member of acetamides.
Oseltamivir (marketed as the product TamifluⓇ), is an antiviral neuraminidase inhibitor used for the treatment and prophylaxis of infection with influenza viruses A (including pandemic H1N1) and B. Oseltamivir exerts its antiviral activity by inhibiting the activity of the viral neuraminidase enzyme found on the surface of the virus, which prevents budding from the host cell, viral replication, and infectivity. The clinical benefit of use of oseltamivir is greatest when administered within 48 hours of the onset of influenza symptoms since effectiveness decreases significantly after that point in time; there is generally no benefit in use beyond 48 hours for healthy, low-risk individuals as influenza is a self-limiting illness. However, antiviral treatment might be beneficial when initiated after 48 hours for patients with severe, complicated or progressive illness or for hospitalized patients. According to the CDC, data from clinical trials and observational studies have demonstrated that early antiviral treatment can shorten the duration of fever and illness symptoms, and may reduce the risk of some complications (including pneumonia and respiratory failure). They recommend the use of oseltamivir in people with a higher risk of developing complications including children younger than 2 years, people over 65 years, people with some chronic conditions or immunosuppression, pregnant women, residents of long term care facilities, and indigenous communities for example. The benefits of oseltamivir use are controversial; a 2014 Cochrane Review of the evidence found that oseltamivir treatment had limited benefit. The authors concluded that oseltamivir use in healthy adults had small, non-specific effects on symptoms (where the time to first alleviation of symptoms was only reduced from 7 to 6.3 days), it had no effect on hospitalizations, and that there was no evidence for any reductions in complications of influenza such as pneumonia. Due to the risk of adverse effects such as nausea, vomiting, psychiatric effects and renal adverse events in adults and vomiting in children, the harms are generally considered to outweigh the small clinical benefit of use of oseltamivir. Notably, in 2017, the World Health Organization downgraded oseltamivir from its essential medicines list from a "core" drug to a "complementary" drug, due to limited cost-effectiveness. Yearly vaccination with the influenza vaccine is still considered the best preventative measure.
Oseltamivir is a Neuraminidase Inhibitor. The mechanism of action of oseltamivir is as a Neuraminidase Inhibitor.
See also: Oseltamivir Acid (has active moiety); Oseltamivir Phosphate (has salt form).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Oseltamivir.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

ethyl (3R,4R,5S)-4-acetamido-5-amino-3-pentan-3-yloxycyclohexene-1-carboxylate
Computed by Lexichem TK 2.7.0 (PubChem release 2024.11.20)

2.1.2 InChI

InChI=1S/C16H28N2O4/c1-5-12(6-2)22-14-9-11(16(20)21-7-3)8-13(17)15(14)18-10(4)19/h9,12-15H,5-8,17H2,1-4H3,(H,18,19)/t13-,14+,15+/m0/s1
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.3 InChIKey

VSZGPKBBMSAYNT-RRFJBIMHSA-N
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.4 SMILES

CCC(CC)O[C@@H]1C=C(C[C@@H]([C@H]1NC(=O)C)N)C(=O)OCC
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C16H28N2O4
Computed by PubChem 2.2 (PubChem release 2024.11.20)

2.3 Other Identifiers

2.3.1 CAS

204255-11-8

2.3.2 UNII

2.3.3 ChEBI ID

2.3.4 ChEMBL ID

2.3.5 DrugBank ID

2.3.6 DSSTox Substance ID

2.3.7 HMDB ID

2.3.8 KEGG ID

2.3.9 Metabolomics Workbench ID

2.3.10 NCI Thesaurus Code

2.3.11 Nikkaji Number

2.3.12 PharmGKB ID

2.3.13 Wikidata

2.3.14 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • GS 4071
  • GS 4104
  • GS-4071
  • GS-4104
  • GS4071
  • GS4104
  • Oseltamivir
  • Tamiflu

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
312.40 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
XLogP3-AA
Property Value
1.1
Reference
Computed by XLogP3 3.0 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Donor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Acceptor Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Rotatable Bond Count
Property Value
8
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Exact Mass
Property Value
312.20490738 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Monoisotopic Mass
Property Value
312.20490738 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Topological Polar Surface Area
Property Value
90.7 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Heavy Atom Count
Property Value
22
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
418
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
3
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

Solid

3.2.2 Solubility

Soluble
6.86e-01 g/L

3.2.3 LogP

1
1

3.2.4 Dissociation Constants

pKa = 7.7 at 25 °C (primary amine)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1233

3.2.5 Collision Cross Section

180.7 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

3.2.6 Other Experimental Properties

Mol wt: 410.40. White crystalline solid /Phosphate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1233

3.3 Chemical Classes

Pharmaceutical

3.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antiviral Agents; Neuraminidase Inhibitors
Human drugs -> Antivirals for systemic use, Neuraminidase inhibitors -> Human pharmacotherapeutic group -> EMA Drug Category
Human drugs -> Antivirals for systemic use -> Human pharmacotherapeutic group -> EMA Drug Category
Other antivirals

4 Spectral Information

4.1 Mass Spectrometry

4.1.1 GC-MS

1 of 2
Source of Spectrum
QC-20-128-1
Copyright
Copyright © 2020-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail
2 of 2
Technique
GC/MS
Source of Spectrum
DigiLab GmbH (C) 2024
Copyright
Copyright © 2024 DigiLab GmbH and Wiley-VCH GmbH. All Rights Reserved.
Thumbnail
Thumbnail

4.1.2 MS-MS

1 of 6
View All
Spectra ID
Ionization Mode
Negative
Top 5 Peaks

58.0299 100

41.99845 2.60

164.07169 2.30

99.05684 1.10

Thumbnail
Thumbnail
2 of 6
View All
Spectra ID
Ionization Mode
Negative
Top 5 Peaks

58.03002 100

240.1115 1.80

164.07169 1.70

41.99852 1.10

Thumbnail
Thumbnail

4.1.3 LC-MS

1 of 41
View All
Authors
Nikiforos Alygizakis, Nikolaos Thomaidis, University of Athens
Instrument
Bruker maXis Impact
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10 eV
Fragmentation Mode
CID
Column Name
Acclaim RSLC C18 2.2um, 2.1x100mm, Thermo
Retention Time
6.9 min
Precursor m/z
313.2122
Precursor Adduct
[M+H]+
Top 5 Peaks

225.1234 999

313.2125 678

208.0967 465

166.0856 253

243.1338 159

Thumbnail
Thumbnail
License
CC BY-SA
2 of 41
View All
Authors
Nikiforos Alygizakis, Nikolaos Thomaidis, University of Athens
Instrument
Bruker maXis Impact
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
20 eV
Fragmentation Mode
CID
Column Name
Acclaim RSLC C18 2.2um, 2.1x100mm, Thermo
Retention Time
6.8 min
Precursor m/z
313.2122
Precursor Adduct
[M+H]+
Top 5 Peaks

166.0854 999

208.0961 365

225.1231 131

120.0437 114

167.0885 89

Thumbnail
Thumbnail
License
CC BY-SA

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

According to FDA prescribing information, oseltamivir is indicated for the treatment of acute, uncomplicated illness due to influenza A and B infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours. In particular, this agent is indicated in adults and children including full-term neonates who present with symptoms typical of influenza when influenza virus is circulating in the community. Efficacy has been demonstrated when treatment is initiated within two days of the first onset of symptoms. Oseltamivir is also indicated for the prophylaxis of influenza in patients one year and older. Specifically, post-exposure prevention in individuals one year of age or older following contact with a clinically diagnosed influenza case when influenza virus is circulating in the community qualifies for such prophylactic therapy. Oseltamivir would only be indicated for post-exposure prevention of influenza in infants less than 1 year of age during a pandemic influenza outbreak.
Treatment of influenzaIn patients one year of age and older who present with symptoms typical of influenza, when influenza virus is circulating in the community. Ebilfumin is indicated for the treatment of infants less than 1 year of age during a pandemic influenza outbreak (see section 5. 2 of the SmPC). The treating physician should take into account the pathogenicity of the circulating strain and the underlying condition of the patient to ensure there is a potential benefit to the child. Prevention of influenzaPost-exposure prevention in individuals 1 year of age or older following contact with a clinically diagnosed influenza case when influenza virus is circulating in the community. The appropriate use of Ebilfumin for prevention of influenza should be determined on a case by case basis by the circumstances and the population requiring protection. In exceptional situations (e. g. in case of a mismatch between the circulating and vaccine virus strains, and a pandemic situation) seasonal prevention could be considered in individuals one year of age or older. Ebilfumin is indicated for post-exposure prevention of influenza in infants less than 1 year of age during a pandemic influenza outbreak (see section 5. 2 of the SmPC). Ebilfumin is not a substitute for influenza vaccination.
Treatment of influenzaTamiflu is indicated in adults and children including full term neonates who present with symptoms typical of influenza, when influenza virus is circulating in the community. Efficacy has been demonstrated when treatment is initiated within two days of first onset of symptoms. Prevention of influenzaPost-exposure prevention in individuals one year of age or older following contact with a clinically diagnosed influenza case when influenza virus is circulating in the community. The appropriate use of Tamiflu for prevention of influenza should be determined on a case-by-case basis by the circumstances and the population requiring protection. In exceptional situations (e. g. in case of a mismatch between the circulating and vaccine virus strains, and a pandemic situation) seasonal prevention could be considered in individuals one year of age or older. Tamiflu is indicated for post-exposure prevention of influenza in infants less than 1 year of age during a pandemic-influenza outbreak. Tamiflu is not a substitute for influenza vaccination. The use of antivirals for the treatment and prevention of influenza should be determined on the basis of official recommendations. Decisions regarding the use of oseltamivir for treatment and prophylaxis should take into consideration what is known about the characteristics of the circulating influenza viruses, available information on influenza drug susceptibility patterns for each season and the impact of the disease in different geographical areas and patient populations.

7.2 LiverTox Summary

Oseltamivir is an inhibitor of the influenza neuraminidase enzyme and is used as therapy and prophylaxis against influenza A and B. Oseltamivir has not been associated with clinically apparent liver injury.

7.3 Drug Classes

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antiviral Agents; Neuraminidase Inhibitors
Antiviral Agents

7.4 Drug Transformations

Oseltamivir has known transformation products that include Oseltamivir acid.
S66 | EAWAGTPS | Parent-Transformation Product Pairs from Eawag | DOI:10.5281/zenodo.3754448

7.5 WHO Essential Medicines

Drug
Drug Classes
Other antivirals
Formulation
Oral - Solid: 30 mg capsule (as phosphate); 45 mg capsule (as phosphate); 75 mg capsule (as phosphate)
Indication
Influenza due to identified seasonal influenza virus

7.6 FDA National Drug Code Directory

7.7 Drug Labels

Drug and label

7.8 Clinical Trials

7.8.1 ClinicalTrials.gov

7.8.2 EU Clinical Trials Register

7.8.3 NIPH Clinical Trials Search of Japan

7.9 EMA Drug Information

1 of 2
Medicine
Category
Human drugs
Therapeutic area
Influenza, Human
Active Substance
oseltamivir
INN/Common name
oseltamivir
Pharmacotherapeutic Classes
Antivirals for systemic use, Neuraminidase inhibitors
Status
This medicine is authorized for use in the European Union
Company
Actavis Group PTC ehf
Market Date
2014-05-22
2 of 2
Medicine
Category
Human drugs
Therapeutic area
Influenza, Human
Active Substance
oseltamivir
INN/Common name
oseltamivir
Pharmacotherapeutic Classes
Antivirals for systemic use
Status
This medicine is authorized for use in the European Union
Company
Roche Registration GmbH
Market Date
2002-06-20

7.10 Therapeutic Uses

Antiviral Agents; Enzyme Inhibitors
National Library of Medicine, SIS; ChemIDplus Record for Oseltamivir (196618-13-0), MESH Heading. Available from, as of March 15, 2006: https://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp
At this time, CDC recommends the use of oseltamivir or zanamivir for the treatment of infection with swine influenza (H1N1) viruses.
CDC; Interim Guidance on Antiviral Recommendations for Patients with Confirmed or Suspected Swine Influenza A (H1N1) Virus Infection and Close Contacts; Available at https://www.cdc.gov/swineflu/recommendations.htm as of April 27, 2009-04-27. CDC; Health Advisory - Investigation and Interim Recommendations: Swine Influenza (H1N1); Available at https://www.cdc.gov/swineflu/pdf/HAN_042509.pdf as of April 27, 2009
MEDICATION: Antiviral; Orally active inhibitor of influenza virus neuraminidase; converted in vivo to the active acid metabolite, GS-4071.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1233
Oseltamivir is indicated for the treatment of uncomplicated acute infection caused by influenza A virus in patients older than 1 year of age who have been symptomatic for no more than 2 days. /Included in US product labeling/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2304
For more Therapeutic Uses (Complete) data for OSELTAMIVIR (8 total), please visit the HSDB record page.

7.11 Drug Warnings

Swine influenza (H1N1) viruses contain a unique combination of gene segments that have not been reported previously among swine or human influenza viruses in the US or elsewhere. The H1N1 viruses are resistant to amantadine and rimantadine but not to oseltamivir or zanamivir.
CDC; Interim Guidance on Antiviral Recommendations for Patients with Confirmed or Suspected Swine Influenza A (H1N1) Virus Infection and Close Contacts; Available at https://www.cdc.gov/swineflu/recommendations.htm as of April 27, 2009-04-27. CDC; Health Advisory - Investigation and Interim Recommendations: Swine Influenza (H1N1); Available at https://www.cdc.gov/swineflu/pdf/HAN_042509.pdf as of April 27, 2009
Adverse effects occurring in 1% or more of adults and at an incidence greater than that with placebo include nausea, vomiting, bronchitis, insomnia, and vertigo. Nausea, with or without vomiting, was most common, usually occurring after the initial dose and resolving within 1-2 days, but resulting in drug discontinuance in less than 1% of adults. Adverse effects occurring in 1% or more of children and at an incidence greater than with placebo include vomiting, abdominal pain, epistaxis, otic disorder, and conjunctivitis. Unlike amantadine and rimantadine, neuraminidase inhibitors like oseltamivir do not appear to adversely affect the CNS.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 767
FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2305
Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza. /Oseltamivir/ has not been shown to prevent such complications.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2811
For more Drug Warnings (Complete) data for OSELTAMIVIR (7 total), please visit the HSDB record page.

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

There have been postmarketing reports of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving oseltamivir. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made but they appear to be uncommon based on oseltamivir. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of oseltamivir to these events has not been established. Influenza can be associated with a variety of neurologic and behavioral symptoms that can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease.

8.2 MeSH Pharmacological Classification

Antiviral Agents
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)
Enzyme Inhibitors
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)

8.3 FDA Pharmacological Classification

1 of 2
FDA UNII
20O93L6F9H
Active Moiety
OSELTAMIVIR
Pharmacological Classes
Established Pharmacologic Class [EPC] - Neuraminidase Inhibitor
Pharmacological Classes
Mechanisms of Action [MoA] - Neuraminidase Inhibitors
FDA Pharmacology Summary
Oseltamivir is a Neuraminidase Inhibitor. The mechanism of action of oseltamivir is as a Neuraminidase Inhibitor.
2 of 2
Non-Proprietary Name
OSELTAMIVIR
Pharmacological Classes
Neuraminidase Inhibitor [EPC]; Neuraminidase Inhibitors [MoA]

8.4 ATC Code

J05AH02
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
S66 | EAWAGTPS | Parent-Transformation Product Pairs from Eawag | DOI:10.5281/zenodo.3754448

J - Antiinfectives for systemic use

J05 - Antivirals for systemic use

J05A - Direct acting antivirals

J05AH - Neuraminidase inhibitors

J05AH02 - Oseltamivir

8.5 Absorption, Distribution and Excretion

Absorption
Oseltamivir is readily absorbed from the gastrointestinal tract after oral administration of oseltamivir phosphate and is extensively converted by predominantly hepatic esterases to the active metabolite oseltamivir carboxylate. At least 75 % of an oral dose reaches the systemic circulation as the active metabolite. Exposure to the pro-drug is less than 5 % relative to the active metabolite. Plasma concentrations of both pro-drug and active metabolite are proportional to dose and are unaffected by co-administration with food. Pharmacokinetic parameters following twice daily dosing of oseltamivir 75mg capsules are as follows: Cmax of oseltamivir and oseltamivir carboxylate were found to be 65ng/mL and 348ng/mL, respectively, while AUC (0-12h) of oseltamivir and oseltamivir carboxylate were found to be 112ng·h/mL and 2719ng·h/mL, respectively.
Route of Elimination
Following absorption, oseltamivir is more than 90 % eliminated through conversion to oseltamivir carboxylate and subsequent elimination entirely through renal excretion. During clinical studies, less than 20 % of oral radiolabelled dose was found to be eliminated in faeces.
Volume of Distribution
The mean volume of distribution at steady state of the oseltamivir carboxylate ranges approximately between 23 and 26 liters in humans, a volume that is roughly equivalent to extracellular body fluid. Since neuraminidase activity is extracellular, oseltamivir carboxylate distributes to all sites of influenza virus spread.
Clearance
Renal clearance (18.8 l/h) of the drug exceeds glomerular filtration rate (7.5 l/h) indicating that tubular secretion occurs in addition to glomerular filtration.
Protein binding: Oseltamivir phosphate: Moderate (42%). Oseltamivir carboxylate: Very low < 3%.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2305
Oseltamivir carboxylate: Volume of distribution is 23 to 26 liters following intravenous administration in 24 subjects.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2305
Oral oseltamivir phosphate is readily absorbed then extensively converted to oseltamivir carboxylate, the active form, predominantly by hepatic esterases. At least 75% of an oral dose reaches the systemic circulation as oseltamivir carboxylate. Less than 5% of an oral dose reaches the systemic circulation as oseltamivir phosphate.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2304
Elimination: Renal: Oseltamivir carboxylate is extensively eliminated by renal excretion (> 99%). Renal clearance (18.8 L/hr) exceeds glomerular filtration rate (7.5 L/hr), indicating that tubular secretion occurs. Fecal: Elimination of an oral radiolabeled dose in < 20% in the feces.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2305
For more Absorption, Distribution and Excretion (Complete) data for OSELTAMIVIR (8 total), please visit the HSDB record page.

8.6 Metabolism / Metabolites

Oseltamivir is extensively converted to the active metabolite, oseltamivir carboxylate, by esterases located predominantly in the liver. Oseltamivir carboxylate is not further metabolized. Neither oseltamivir nor oseltamivir carboxylate is a substrate for, or inhibitor of, cytochrome P450 isoforms. No phase 2 conjugates of either compound have been identified in vivo.
Oseltamivir is extensively converted to oseltamivir carboxylate by esterases located predominantly in the liver. Neither oseltamivir nor oseltamivir carboxylate is a substrate for, or inhibitor of, cytochrome p450 isoforms.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2810
Biotransformation: Hepatic; oseltamivir, ethyl ester prodrug, undergoes extensive hydrolysis to the active aster form, oseltamivir carboxylate.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2305

8.7 Biological Half-Life

Plasma concentrations of oseltamivir declined with a half-life of 1 to 3 hours in most subjects after oral administration, although plasma concentrations of oseltamivir carboxylate declined with a half-life of 6 to 10 hours in most subjects after oral administration.
Elimination: 1 to 3 hours for oseltamivir and 6 to 10 hours for oseltamivir carboxylate.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2305

8.8 Mechanism of Action

Oseltamivir phosphate is a pro-drug of the active metabolite (oseltamivir carboxylate) which is a potent and selective inhibitor of influenza virus neuraminidase enzymes, which are glycoproteins found on the virion surface. Viral neuraminidase enzyme activity is important for viral entry into uninfected cells, for the release of recently formed virus particles from infected cells, and for the further spread of the infectious virus in the body. Oseltamivir activity reduces viral shedding and infectivity. Oseltamivir is effective agaisnt viral neuraminidases of influenza A (including pandemic H1N1) and influenza B.
Oseltamivir is an ethyl ester prodrug requiring ester hydrolysis for conversion to the active form, oseltamivir carboxylate. The proposed mechanism of action of oseltamivir is inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2810

8.9 Human Metabolite Information

8.9.1 Cellular Locations

  • Cytoplasm
  • Extracellular
  • Membrane

8.10 Transformations

9 Use and Manufacturing

9.1 Uses

MEDICATION: Antiviral /Oseltamivir phosphate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1233
Antiviral Agents; Enzyme Inhibitors
National Library of Medicine, SIS; ChemIDplus Record for Oseltamivir (196618-13-0), MESH Heading. Available from, as of March 15, 2006: https://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp

Use (kg) in Switzerland (2009): >100

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

Consumption (g per capita) in Switzerland (2009): 0.013

Consumption (g per capita; approx.) in Germany (2009): 0.012

Excretion rate: 0.1

Calculated removal (%): 22.1

9.1.1 Use Classification

Human drugs -> Antivirals for systemic use, Neuraminidase inhibitors -> Human pharmacotherapeutic group -> EMA Drug Category
Human drugs -> Antivirals for systemic use -> Human pharmacotherapeutic group -> EMA Drug Category
Pharmaceuticals -> Antiinfectives for systemic use -> Antivirals for systemic use -> Direct acting antivirals -> Neuraminidase inhibitors
S66 | EAWAGTPS | Parent-Transformation Product Pairs from Eawag | DOI:10.5281/zenodo.3754448

9.2 Methods of Manufacturing

N. W. Bischofberger et al., US Patent 5763483 (1998 to Gilead Sci.).
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1233

9.3 Formulations / Preparations

Oral: Capsules: 75 mg (of oseltamivir) (Tamiflu), (Roche); For Suspension: 12 mg (of oseltamivir) per mL (Tamiflu), (Roche). /Oseltamivir phosphate/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 768

10 Safety and Hazards

10.1 Accidental Release Measures

10.1.1 Disposal Methods

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

10.2 Handling and Storage

10.2.1 Storage Conditions

Store dry powder at 25 °C (77 °F); excursions permitted to 15 deg to 30 °C (59 deg to 86 °F).
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2813
Store the capsules at 25 °C (77 °F); excursions permitted to 15 deg to 30 °C (59 deg to 86 °F).
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2813

10.3 Regulatory Information

10.3.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl oseltamivir phosphate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Oseltamivir phosphate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 3, 2006: https://www.fda.gov/cder/ob/

11 Toxicity

11.1 Toxicological Information

11.1.1 USGS Health-Based Screening Levels for Evaluating Water-Quality

Chemical
Oseltamivir
Chemical Classes
Pharmaceutical
Reference
Smith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP

11.1.2 Hepatotoxicity

In clinical trials of oseltamivir, serum aminotransferase elevations occurred in 2% of treated subjects, but were asymptomatic and transient in all and there were no reports of clinically apparent liver injury with jaundice. The rates of ALT elevations with oseltamivir were generally similar to those treated with placebo or with a comparative agents. Since its approval in 1999, oseltamivir has been widely used during influenza seasonal outbreaks. There have been a few, isolated reports of mild liver injury in patients receiving oseltamivir, but the relationship of the injury with oseltamivir has not always been very convincingly shown. There have been no reports of acute liver failure or chronic liver disease attributed to oseltamivir use. Furthermore, a proportion of patients with influenza have serum enzyme elevations and even mild jaundice during the acute illness, independent of any therapy.

Likelihood score: D (possible rare cause of clinically apparent liver injury).

11.1.3 Drug Induced Liver Injury

Compound
oseltamivir
DILI Annotation
Ambiguous DILI-concern
Severity Grade
3
Label Section
Adverse reactions
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

11.1.4 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Limited data indicate that oseltamivir and its active metabolite are poorly excreted into breastmilk. Maternal dosages of 150 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants. Infants over 2 weeks of age can receive oseltamivir directly in doses much larger than those in breastmilk.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

11.1.5 Interactions

Concomitant administration /with probenecid/ results in an approximate two-fold increase in the active metabolite due to a decrease in active anionic tubular secretion in the kidney.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2305
In vitro studies demonstrate that neither oseltamivir nor oseltamivir carboxylate is a good substrate for P450 mixed-function oxidases or for glucuronyl transferases. Cimetidine, a non-specific inhibitor of cytochrome P450 isoforms and competitor for renal tubular secretion of basic or cationic drugs, has no effect on plasma levels of oseltamivir or oseltamivir carboxylate.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2811
Coadministration with amoxicillin does not alter plasma levels of either compound, indicating that competition for the anionic secretion pathway is weak.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2811

11.1.6 Antidote and Emergency Treatment

/SRP:/ Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison A and B/
Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p. 139
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/
Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p. 139

11.1.7 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ In a 2-week study in unweaned rats, administration of a single dose of 1000 mg/kg oseltamivir phosphate to 7- day-old rats resulted in deaths associated with unusually high exposure to the prodrug. However, at 2000 mg/kg, there were no deaths or other significant effects in 14-day-old unweaned rats. Further follow-up investigations of the unexpected deaths of 7-day-old rats at 1000 mg/kg revealed that the concentrations of the prodrug in the brains were approximately 1500-fold those of the brains of adult rats administered the same oral dose of 1000 mg/kg, and those of the active metabolite were approximately 3-fold higher. Plasma levels of the prodrug were 10-fold higher in 7-day-old rats as compared with adult rats. These observations suggest that the levels of oseltamivir in the brains of rats decrease with increasing age and most likely reflect the maturation stage of the blood-brain barrier. No adverse effects occurred at 500 mg/kg/day administered to 7- to 21-day-old rats.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2812
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ A 26-week dermal carcinogenicity study of oseltamivir carboxylate in FVB/Tg.AC transgenic mice was negative. The animals were dosed at 40, 140, 400 or 780 mg/kg/day in two divided doses. The highest dose represents the maximum feasible dose based on the solubility of the compound in the control vehicle. A positive control, tetradecanoyl phorbol-13-acetate administered at 2.5 ug per dose three times per week gave a positive response.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2811
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In a rat study, minimal maternal toxicity ws reported with 1500 mg/kg per day orally and no maternal toxicities were reported with 50 and 250 mg/kg per day orally. In a rabbit study, slight and marked maternal toxicities were observed, respectively, with 150 and 500 mg/kg per day and not maternal toxicities with 50 mg/kg per day. In the rat and rabbit study there was a dose-dependent increase in the incidence rates of a variety of minor skeleton abnormalities and variants in the exposed offspring. However, the individual incidence rate of each skeletal abnormality or variant remained within the background rates of occurrence in the species studied.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2305
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Doses of oseltamivir administered to female rats 2 weeks before mating, during mating and until Day 6 of pregnancy were 50, 250, and 1500 mg/kg per day. Doses of oseltamivir were administered to male rats 4 weeks before mating, during, and for 2 weeks after mating. oseltamivir lacked an effect of fertility, mating performance, or early embryonic development at any dose level.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2305
/GENOTOXICITY/ Oseltamivir was found to be non-mutagenic in the Ames test and the human lymphocyte chromosome assay with and without enzymatic activation and negative in the mouse micronucleus test. It was found to be positive in a Syrian Hamster Embryo (SHE) cell transformation test. Oseltamivir carboxylate was non-mutagenic in the Ames test and the L5178Y mouse lymphoma assay with and without enzymatic activation and negative in the SHE cell transformation test.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2811

11.1.8 Protein Binding

The binding of the active oseltamivir carboxylate metabolite to human plasma protein is negligible at approximately 3 % while the binding of oseltamivir to human plasma protein is 42%, which is insufficient to cause significant displacement-based drug interactions.

11.2 Ecological Information

11.2.1 Environmental Fate / Exposure Summary

Oseltamivir's production and use as an antiviral drug for the treatment of individuals with influenza may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.3X10-8 mm Hg at 25 °C indicates oseltamivir will exist solely in the particulate phase in the atmosphere. Particulate-phase oseltamivir will be removed from the atmosphere by wet or dry deposition. Oseltamivir does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, oseltamivir is expected to have moderate mobility based upon an estimated Koc of 340. The pKa of oseltamivir is 7.7 (primary amine), indicating that this compound will exist partially as a cation in the environment and cations generally have lower mobility in soil than their neutral counterparts. Volatilization from moist soil surfaces is not expected to be an important fate process because cations do not volatilize and based upon an estimated Henry's Law constant of 2.9X10-16 atm-cu m/mole for the neutral species. Biodegradation data were not available. If released into water, oseltamivir is expected to adsorb slightly to suspended solids and sediment based upon the estimated Koc. However, adsorption may be stronger than this Koc value suggests since cations generally adsorb to sediment more strongly than their neutral counterparts. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant and the fact that cations do not volatilize. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. A base-catalyzed second-order hydrolysis rate constant of 2.0X10-3 L/mole-sec was estimated using a structure estimation method; this corresponds to half-lives of 110 and 10 years at pH values of 7 and 8, respectively. Occupational exposure to oseltamivir may occur through inhalation and dermal contact with this compound at workplaces where oseltamivir is produced or used. Exposure to oseltamivir among the general population may be limited to those administered this substance as a drug. (SRC)

11.2.2 Artificial Pollution Sources

Oseltamivir's production and use as an antiviral drug for the treatment of individuals with influenza(1) may result in its release to the environment through various waste streams(SRC).
(1) O'Neil MJ, ed; The Merck Index. 13th ed, Whitehouse Station, NJ: Merck and Co., Inc., p 1233 (2001)

11.2.3 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 340(SRC), determined from a structure estimation method(2), indicates that oseltamivir is expected to have moderate mobility in soil(SRC). The pKa of oseltamivir is 7.7 (primary amine)(3), indicating that this compound will exist partially as a cation in the environment and cations generally have lower mobility in soil than their neutral counterparts(4). Volatilization of oseltamivir from moist soil surfaces is not expected to be an important fate process(SRC) because cations do not volatilize and based on an estimated Henry's Law constant of 2.9X10-16 atm-cu m/mole(SRC), calculated using a fragment constant estimation method(5). Oseltamivir is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.3X10-8 mm Hg(SRC), determined from a fragment constant method(6). Biodegradation data were not available(SRC, 2006).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992)
(3) O'Neil MJ, ed; The Merck Index. 13th ed, Whitehouse Station, NJ: Merck and Co., Inc., p 1233 (2001)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(5) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(6) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 340(SRC), determined from a structure estimation method(2), indicates that oseltamivir is expected to adsorb slightly to suspended solids and sediment(SRC). The pKa of oseltamivir is 7.7 (primary amine)(3), indicating that this compound will exist partially as a cation in the environment and cations generally adsorb to sediment more strongly than their neutral counterparts(4). Volatilization from water surfaces is not expected(5) because cations do not volatilize and based upon an estimated Henry's Law constant of 2.9X10-16 atm-cu m/mole(SRC), developed using a fragment constant estimation method(6). According to a classification scheme(7), an estimated BCF of 3(SRC), from an estimated log Kow of 0.95(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2006).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992)
(3) O'Neil MJ, ed; The Merck Index. 13th ed, Whitehouse Station, NJ: Merck and Co., Inc., p 1233 (2001)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(5) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990)
(6) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(7) Franke C et al; Chemosphere 29: 1501-14 (1994)
(8) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), oseltamivir, which has an estimated vapor pressure of 1.3X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase oseltamivir may be removed from the air by wet or dry deposition(SRC). Oseltamivir does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)

11.2.4 Environmental Abiotic Degradation

A base-catalyzed second-order hydrolysis rate constant of 2.0X10-3 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 110 and 10 years at pH values of 7 and 8, respectively(1). Oseltamivir does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Mill T et al; Environmental Fate and Exposure Studies Development of a PC-SAR for Hydrolysis: Esters, Alkyl Halides and Epoxides. EPA Contract No. 68-02-4254. Menlo Park, CA: SRI International (1987)

11.2.5 Environmental Bioconcentration

An estimated BCF of 3 was calculated for oseltamivir(SRC), using an estimated log Kow of 0.95(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
(1) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995)
(2) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

11.2.6 Soil Adsorption / Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc of oseltamivir can be estimated to be 340(SRC). According to a classification scheme(2), this estimated Koc value suggests that oseltamivir is expected to have moderate mobility in soil. The pKa of oseltamivir is 7.7 (primary amine)(3), indicating that this compound will exist partially as a cation in the environment and cations generally adsorb to soil and sediment more strongly than their neutral counterparts(4).
(1) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992)
(2) Swann RL et al; Res Rev 85: 17-28 (1983)
(3) O'Neil MJ, ed; The Merck Index. 13th ed, Whitehouse Station, NJ: Merck and Co., Inc., p 1233 (2001)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)

11.2.7 Volatilization from Water / Soil

The Henry's Law constant for oseltamivir is estimated as 2.9X10-16 atm-cu m/mole(SRC) using a fragment constant estimation method(1). The pKa of oseltamivir is 7.7 (primary amine)(2), indicating that this compound will exist partially as a cation in the environment. Based on this Henry's Law constant and the fact that cations do not volatilize, oseltamivir is expected to be essentially nonvolatile from moist soil and water surfaces(3). Oseltamivir is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.3X10-8 mm Hg(SRC), determined from a fragment constant method(4).
(1) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(2) O'Neil MJ, ed; The Merck Index. 13th ed, Whitehouse Station, NJ: Merck and Co., Inc., p 1233 (2001)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)
(4) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)

11.2.8 Environmental Water Concentrations

While data specific to oseltamivir were not located(SRC, 2006), 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).
(1) Heberer T; Tox Lett 131: 5-17 (2002)
(2) Koplin DW et al; Environ Sci Toxicol 36: 1202-211 (2002)

11.2.9 Milk Concentrations

It is not known whether oseltamivir is distributed into human breast milk. Oseltamivir and oseltamivir carboxylate are distributed into the milk of lactating rats.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2305

11.2.10 Probable Routes of Human Exposure

Occupational exposure to oseltamivir may occur through inhalation and dermal contact with this compound at workplaces where oseltamivir is produced or used. Exposure to oseltamivir among the general population may be limited to those administered this substance as a drug. (SRC)

12 Associated Disorders and Diseases

13 Literature

13.1 Consolidated References

13.2 NLM Curated PubMed Citations

13.3 Springer Nature References

13.4 Thieme References

13.5 Wiley References

13.6 Chemical Co-Occurrences in Literature

13.7 Chemical-Gene Co-Occurrences in Literature

13.8 Chemical-Disease Co-Occurrences in Literature

14 Patents

14.1 Depositor-Supplied Patent Identifiers

14.2 WIPO PATENTSCOPE

14.3 Chemical Co-Occurrences in Patents

14.4 Chemical-Disease Co-Occurrences in Patents

14.5 Chemical-Gene Co-Occurrences in Patents

15 Interactions and Pathways

15.1 Chemical-Target Interactions

15.2 Drug-Drug Interactions

15.3 Drug-Food Interactions

Take with or without food. Co-administration with food does not affect pharmacokinetics but may enhance tolerability.

16 Biological Test Results

16.1 BioAssay Results

17 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

18 Classification

18.1 MeSH Tree

18.2 NCI Thesaurus Tree

18.3 ChEBI Ontology

18.4 KEGG: ATC

18.5 KEGG: Drug Groups

18.6 KEGG : Antimicrobials

18.7 WHO ATC Classification System

18.8 FDA Pharm Classes

18.9 ChemIDplus

18.10 ChEMBL Target Tree

18.11 NORMAN Suspect List Exchange Classification

18.12 CCSBase Classification

18.13 EPA DSSTox Classification

18.14 LOTUS Tree

18.15 MolGenie Organic Chemistry Ontology

19 Information Sources

  1. BindingDB
    LICENSE
    All data curated by BindingDB staff are provided under the Creative Commons Attribution 3.0 License (https://creativecommons.org/licenses/by/3.0/us/).
    https://www.bindingdb.org/rwd/bind/info.jsp
  2. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  3. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  4. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  5. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  6. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  7. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  8. Hazardous Substances Data Bank (HSDB)
  9. Human Metabolome Database (HMDB)
    LICENSE
    HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  10. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  11. ChEBI
  12. FDA Pharm Classes
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  13. LiverTox
  14. LOTUS - the natural products occurrence database
    LICENSE
    The code for LOTUS is released under the GNU General Public License v3.0.
    https://lotus.nprod.net/
  15. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  16. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  17. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  18. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  19. Therapeutic Target Database (TTD)
  20. DailyMed
  21. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  22. European Medicines Agency (EMA)
    LICENSE
    Information on the European Medicines Agency's (EMA) website is subject to a disclaimer and copyright and limited reproduction notices.
    https://www.ema.europa.eu/en/about-us/legal-notice
  23. Drugs and Lactation Database (LactMed)
  24. WHO Model Lists of Essential Medicines
    LICENSE
    Permission from WHO is not required for the use of WHO materials issued under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Intergovernmental Organization (CC BY-NC-SA 3.0 IGO) license.
    https://www.who.int/about/policies/publishing/copyright
  25. EU Clinical Trials Register
  26. 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/
    Oseltamivir
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  27. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  28. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  29. Japan Chemical Substance Dictionary (Nikkaji)
  30. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
  31. Natural Product Activity and Species Source (NPASS)
  32. MassBank Europe
  33. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  34. Metabolomics Workbench
  35. NIPH Clinical Trials Search of Japan
  36. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  37. SpectraBase
  38. Springer Nature
  39. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  40. USGS Health-Based Screening Levels for Evaluating Water-Quality Data
  41. Wikidata
  42. Wikipedia
  43. Wiley
  44. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  45. PubChem
  46. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  47. PATENTSCOPE (WIPO)
  48. NCBI
CONTENTS