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Mycophenolate Mofetil

PubChem CID
5281078
Structure
Mycophenolate Mofetil_small.png
Mycophenolate Mofetil_3D_Structure.png
Mycophenolate Mofetil__Crystal_Structure.png
Molecular Formula
Synonyms
  • mycophenolate mofetil
  • 128794-94-5
  • CellCept
  • 115007-34-6
  • Myfenax
Molecular Weight
433.5 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-26
  • Modify:
    2024-12-28
Description
Mycophenolate mofetil is a carboxylic ester resulting from the formal condensation between the carboxylic acid group of mycophenolic acid and the hydroxy group of 2-(morpholin-4-yl)ethanol. In the liver, it is metabolised to mycophenolic acid, an immunosuppressant for which it is a prodrug. It is widely used to prevent tissue rejection following organ transplants as well as for the treatment of certain autoimmune diseases. It has a role as an immunosuppressive agent, a prodrug, an EC 1.1.1.205 (IMP dehydrogenase) inhibitor and an anticoronaviral agent. It is a gamma-lactone, a member of phenols, an ether, a carboxylic ester and a tertiary amino compound. It is functionally related to a mycophenolic acid and a 2-(morpholin-4-yl)ethanol.
Mycophenolate mofetil, also known as MMF or CellCept, is a prodrug of mycophenolic acid, and classified as a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH). This drug is an immunosuppressant combined with drugs such as [Cyclosporine] and corticosteroids to prevent organ rejection after hepatic, renal, and cardiac transplants. It is marketed by Roche Pharmaceuticals and was granted FDA approval for the prophylaxis of transplant rejection in 1995. In addition to the above uses, mycophenolate mofetil has also been studied for the treatment of nephritis and other complications of autoimmune diseases. Unlike another immunosuppressant class, the calcineurin inhibitors, MMF generally does not cause nephrotoxicity or fibrosis. Previously, mycophenolic acid (MPA) was administered to individuals with autoimmune diseases beginning in the 1970s, but was discontinued due to gastrointestinal effects and concerns over carcinogenicity. The new semi-synthetic 2-morpholinoethyl ester of MPA was synthesized to avoid the gastrointestinal effects associated with the administration of MPA. It demonstrates an increased bioavailability, a higher efficacy, and reduced gastrointestinal effects when compared to MPA.
Mycophenolate Mofetil is the morpholinoethyl ester of mycophenolic acid (MPA) with potent immunosuppressive properties. Mycophenolate stops T-cell and B-cell proliferation through selective inhibition of the de novo pathway of purine biosynthesis. In vivo, the active metabolite, MPA, reversibly inhibits inosine 5'-monophosphate dehydrogenase, an enzyme involved in the de novo synthesis of guanine nucleotides. MPA displays high lymphocyte specificity and cytotoxicity due to the higher dependence of activated lymphocytes on both salvage and de novo synthesis of guanine nucleotides relative to other cell types. (NCI04)
See also: Mycophenolic Acid (has active moiety); Mycophenolate Mofetil Hydrochloride (has salt form).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Mycophenolate Mofetil.png

1.2 3D Conformer

1.3 Crystal Structures

1 of 2
View All
CCDC Number
Crystal Structure Data
Crystal Structure Depiction
Crystal Structure Depiction

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

2-morpholin-4-ylethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoate
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C23H31NO7/c1-15(5-7-19(25)30-13-10-24-8-11-29-12-9-24)4-6-17-21(26)20-18(14-31-23(20)27)16(2)22(17)28-3/h4,26H,5-14H2,1-3H3/b15-4+
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

RTGDFNSFWBGLEC-SYZQJQIISA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CC1=C2COC(=O)C2=C(C(=C1OC)C/C=C(\C)/CCC(=O)OCCN3CCOCC3)O
Computed by OEChem 2.3.0 (PubChem release 2021.10.14)

2.2 Molecular Formula

C23H31NO7
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

115007-34-6

2.3.2 Deprecated CAS

115007-34-6, 140401-05-4
140401-05-4

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 HMDB ID

2.3.10 KEGG ID

2.3.11 Metabolomics Workbench ID

2.3.12 NCI Thesaurus Code

2.3.13 Nikkaji Number

2.3.14 NSC Number

2.3.15 PharmGKB ID

2.3.16 Pharos Ligand ID

2.3.17 RXCUI

2.3.18 Wikidata

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Cellcept
  • Mofetil Hydrochloride, Mycophenolate
  • Mofetil, Mycophenolate
  • mycophenolate mofetil
  • mycophenolate mofetil hydrochloride
  • Mycophenolate Sodium
  • Mycophenolate, Sodium
  • Mycophenolic Acid
  • mycophenolic acid morpholinoethyl ester
  • myfortic
  • RS 61443
  • RS-61443
  • RS61443
  • Sodium Mycophenolate

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
433.5 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
3.2
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
8
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
10
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
433.21005233 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
433.21005233 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
94.5Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
31
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
646
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
0
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
1
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 Color / Form

White to off-white crystalline powder
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. 1132

3.2.3 Boiling Point

3.2.4 Melting Point

93-94
93-94 °C
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. 1132

3.2.5 Solubility

43μg/mL
Freely soluble in acetone, soluble in methanol, and sparingly soluble in ethanol
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2751
In water, 43 mg/L at pH 7.4, temp not specified
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2751
9.50e-02 g/L

3.2.6 LogP

2.5
log Kow = 2.38 at pH 7.4
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. 1132
2.5

3.2.7 Dissociation Constants

pKa
5.6 for the morpholino group and 8.5 for the phenolic group
pKa1 = 5.6 (tertiary amine); pKa2 = 8.5 (phenol)
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2751

3.2.8 Collision Cross Section

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

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals
S10 | SWISSPHARMA | Pharmaceutical List with Consumption Data | DOI:10.5281/zenodo.2623484
Pharmaceuticals -> Antibiotics
S6 | ITNANTIBIOTIC | Antibiotic List from the ITN MSCA ANSWER | DOI:10.5281/zenodo.2621956
Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
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; Discontinued; Active ingredient (MYCOPHENOLATE MOFETIL)
Human drug -> Prescription
Human drugs -> Immunosuppressants -> Human pharmacotherapeutic group -> EMA Drug Category

4 Spectral Information

4.1 Mass Spectrometry

4.1.1 GC-MS

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

Spectra ID
Ionization Mode
positive
Top 5 Peaks

434.220398 100

435.222931 83.96

114.092903 54.77

195.065994 43.32

207.065994 36.26

Thumbnail
Thumbnail
Notes
instrument=qTof

4.1.3 LC-MS

MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
434.217
Instrument
qTof
Ionization Mode
positive
Top 5 Peaks

434.220398 100

435.222931 83.96

114.092903 54.77

195.065994 43.32

207.065994 36.26

Thumbnail
Thumbnail

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Mycophenolate mofetil is indicated in combination with other immunosuppressants to prevent the rejection of kidney, heart, or liver transplants in adult and pediatric patients ≥3 months old. Mycophenolate mofetil may also be used off-label as a second-line treatment for autoimmune hepatitis that has not responded adequately to first-line therapy. Other off-label uses of this drug include lupus-associated nephritis and dermatitis in children.
CellCept is indicated in combination with ciclosporin and corticosteroids for the prophylaxis of acute transplant rejection in patients receiving allogeneic renal, cardiac or hepatic transplants.

7.2 FDA Medication Guides

Drug
Active Ingredient
MYCOPHENOLATE MOFETIL
Form;Route
CAPSULE;ORAL
Company
ROCHE PALO
Date
8/10/22
Drug
Active Ingredient
MYCOPHENOLATE MOFETIL
Form;Route
TABLET;ORAL
Company
ROCHE PALO
Date
8/10/22
Drug
Active Ingredient
Form;Route
INJECTABLE;INJECTION
Company
ROCHE PALO
Date
8/10/22
Drug
Active Ingredient
MYCOPHENOLATE MOFETIL
Form;Route
FOR SUSPENSION;ORAL
Company
ROCHE PALO
Date
8/10/22

7.3 FDA Approved Drugs

7.4 FDA Orange Book

7.5 FDA National Drug Code Directory

7.6 Drug Labels

Drug and label
Active ingredient and drug

7.7 Clinical Trials

7.7.1 ClinicalTrials.gov

7.7.2 EU Clinical Trials Register

7.7.3 NIPH Clinical Trials Search of Japan

7.8 EMA Drug Information

1 of 4
View All
Medicine
Category
Human drugs
Therapeutic area
Graft Rejection
Active Substance
mycophenolate mofetil
INN/Common name
mycophenolate mofetil
Pharmacotherapeutic Classes
Immunosuppressants
Status
This medicine is authorized for use in the European Union
Company
Roche Registration GmbH
Market Date
1996-02-14
2 of 4
View All
Medicine
Category
Human drugs
Therapeutic area
Graft Rejection
Active Substance
mycophenolate mofetil
INN/Common name
mycophenolate mofetil
Pharmacotherapeutic Classes
Immunosuppressants
Status
This medicine is authorized for use in the European Union
Company
Teva B.V.
Market Date
2008-02-21

7.9 Therapeutic Uses

Anti-Inflammatory Agents, Non-Steroidal, Antineoplastic Agents, Dermatologic Agents, Enzyme Inhibitors, Immunosuppressive Agents
National Library of Medicine, SIS; ChemIDplus Record for Mycophenolate Mofetil (128794-94-5), MESH Heading. Available from, as of March 15, 2006: https://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp
MEDICATION: Immunosuppressant
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. 1132
Mycophenolate is indicated, in combination with cyclosporine and corticosteroids, for prevention of rejection of allogeneic cardiac, hepatic and renal transplants. /Included in US product labeling/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2141
Mycophenolate is indicated for the treatment of lupus nephritis. /NOT included in US product labeling/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2141

7.10 Drug Warnings

Severe GI bleeding (requiring hospitalization) has occurred in 3, 1.7, or 5.4% of renal, cardiac, or hepatic transplant recipients, respectively, receiving 3-g daily dosages of mycophenolate mofetil in clinical studies. Because mycophenolate mofetil has been associated rarely with an increased incidence of adverse GI effects (e.g., ulceration, hemorrhage, perforation), the drug should be administered with caution in patients with active serious GI disease.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 3676
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. 2142
Severe neutropenia (i.e., absolute neutrophil counts (ANC) of less than 500/cu mm) has been reported in up to 2, 2.8, or 3.6% of renal, cardiac, or hepatic allograft recipients, respectively, receiving 3-g daily dosages of mycophenolate mofetil. Neutropenia has been observed most frequently between 31-180 days post-transplant in patients receiving immunosuppressive therapy for the prevention of rejection of kidney, heart, or liver allograft. Neutropenia may be related to mycophenolate mofetil, concomitant therapies, viral infection, or a combination of these causes.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 3676
Potential for the development of lymphoma and other malignancies, particularly of the skin, which may result from immunosuppression. Because of the increased risk for skin cancer, patients should be advised to limit their exposure to sunlight or other UV light by wearing protective clothing and using sunscreen with a high protection factor. Lymphoproliferative disease or lymphoma occurred in 0.4-1% of allograft recipients receiving mycophenolate mofetil in conjunction with other immunosuppressive agents in clinical studies. Non-melanoma skin carcinoma was reported in 1.6-4.2% of patients while other types of malignancy were reported in 0.7-2.1% of patients.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 3675
For more Drug Warnings (Complete) data for MYCOPHENOLATE MOFETIL (15 total), please visit the HSDB record page.

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Mycophenolate mofetil is a prodrug of mycophenolic acid (MPA). The active form of mycophenolate, MPA, prevents the proliferation of immune cells and the formation of antibodies that cause transplant rejection. The above effects lead to higher rates of successful transplantation, avoiding the devastating effects of graft rejection.

8.2 MeSH Pharmacological Classification

Antibiotics, Antineoplastic
Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. (See all compounds classified as Antibiotics, Antineoplastic.)
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.)
Antibiotics, Antitubercular
Substances obtained from various species of microorganisms that are, alone or in combination with other agents, of use in treating various forms of tuberculosis; most of these agents are merely bacteriostatic, induce resistance in the organisms, and may be toxic. (See all compounds classified as Antibiotics, Antitubercular.)

8.3 FDA Pharmacological Classification

Non-Proprietary Name
MYCOPHENOLATE MOFETIL
Pharmacological Classes
Antimetabolite Immunosuppressant [EPC]

8.4 ATC Code

L04AA06

8.5 Absorption, Distribution and Excretion

Absorption
Mycophenolate mofetil is rapidly absorbed in the small intestine. The maximum concentration of its active metabolite, MPA, is attained 60 to 90 minutes following an oral dose. The average bioavailability of orally administered mycophenolate mofetil in a pharmacokinetic study of 12 healthy patients was 94%. In healthy volunteers, the Cmax of mycophenolate mofetil was 24.5 (±9.5)μg/mL. In renal transplant patients 5 days post-transplant, Cmax was 12.0 (±3.82) μg/mL, increasing to 24.1 (±12.1)μg/mL 3 months after transplantation. AUC values were 63.9 (±16.2) μg•h/mL in healthy volunteers after one dose, and 40.8 (±11.4) μg•h/mL, and 65.3 (±35.4)μg•h/mL 5 days and 3 months after a renal transplant, respectively. The absorption of mycophenolate mofetil is not affected by food.
Route of Elimination
A small amount of drug is excreted as MPA in the urine (less than 1%). When mycophenolate mofetil was given orally in a pharmacokinetic study, it was found to be 93% excreted in urine and 6% excreted in feces. Approximately 87% of the entire administered dose is found to be excreted in the urine as MPAG, an inactive metabolite.
Volume of Distribution
The volume of distribution of mycophenolate mofetil is 3.6 (±1.5) to 4.0 (±1.2) L/kg.
Clearance
Plasma clearance of mycophenolate mofetil is 193 mL/min after an oral dose and 177 (±31) mL/min after an intravenous dose.
/Absorption/ is rapid and extensive after oral administration.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2142
In 12 healthy volunteers, the mean absolute bioavailability of oral mycophenolate mofetil relative to intravenous mycophenolate mofetil (based on MPA AUC) was 94%. The area under the plasma-concentration time curve (AUC) for MPA appears to increase in a dose-proportional fashion in renal transplant patients receiving multiple doses of mycophenolate mofetil up to a daily dose of 3 g.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2752
Protein binding: To plasma albumin: High (97% for mycophenolic acid (MPA) at concentration ranges normally seen in stable renal transplant patients). At higher mycophenolic acid glucuronide (MPAG) concentrations (e.g., in patients with renal impairment or delayed graft function), binding of MPA may be decreased as a result of competition between MPA and MPAG for binding sites.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2142
The mean (+/-SD) apparent volume of distribution of MPA in 12 healthy volunteers is approximately 3.6 (+/-1.5) and 4.0 (+/-1.2) L/kg following intravenous and oral administration, respectively. MPA, at clinically relevant concentrations, is 97% bound to plasma albumin. MPAG is 82% bound to plasma albumin at MPAG concentration ranges that are normally seen in stable renal transplant patients; however, at higher MPAG concentrations (observed in patients with renal impairment or delayed renal graft function), the binding of MPA may be reduced as a result of competition between MPAG and MPA for protein binding. Mean blood to plasma ratio of radioactivity concentrations was approximately 0.6 indicating that MPA and MPAG do not extensively distribute into the cellular fractions of blood.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2752
For more Absorption, Distribution and Excretion (Complete) data for MYCOPHENOLATE MOFETIL (9 total), please visit the HSDB record page.

8.6 Metabolism / Metabolites

After both oral and intravenous administration mycophenolate mofetil is entirely metabolized by liver carboxylesterases 1 and 2 to mycophenolic acid (MPA), the active parent drug. It is then metabolized by the enzyme glucuronyl transferase, producing the inactive phenolic glucuronide of MPA (MPAG). The glucuronide metabolite is important, as it is then converted to MPA through enterohepatic recirculation. Mycophenolate mofetil that escapes metabolism in the intestine enters the liver via the portal vein and is transformed to pharmacologically active MPA in the liver cells.N-(2-carboxymethyl)-morpholine, N-(2-hydroxyethyl)-morpholine, and the N-oxide portion of N-(2-hydroxyethyl)-morpholine are additional metabolites of MMF occurring in the intestine as a result of liver carboxylesterase 2 activity. UGT1A9 and UGT2B7 in the liver are the major enzymes contributing to the metabolism of MPA in addition to other UGT enzymes, which also play a role in MPA metabolism. The four major metabolites of MPA are 7-O-MPA-β-glucuronide (MPAG, inactive), MPA acyl-glucuronide (AcMPAG), produced by uridine 5ʹ-diphosphate glucuronosyltransferases (UGT) activities, 7-O-MPA glucoside produced via UGT, and small amounts 6-O-des-methyl-MPA (DM-MPA) via CYP3A4/5 and CYP2C8 enzymes.
Following oral and intravenous dosing, mycophenolate mofetil undergoes complete metabolism to MPA /mycophenolic acid/, the active metabolite. Metabolism to MPA occurs presystemically after oral dosing. MPA is metabolized principally by glucuronyl transferase to form the phenolic glucuronide of MPA (MPAG) which is not pharmacologically active. In vivo, MPAG is converted to MPA via enterohepatic recirculation. The following metabolites of the 2- hydroxyethyl-morpholino moiety are also recovered in the urine following oral administration of mycophenolate mofetil to healthy subjects: N-(2-carboxymethyl)-morpholine, N-(2- hydroxyethyl)-morpholine, and the N-oxide of N-(2-hydroxyethyl)-morpholine.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2752

8.7 Biological Half-Life

The average apparent half-life of mycophenolate mofetil is 17.9 (±6.5) hours after oral administration and 16.6 (±5.8) hours after intravenous administration.
For mycophenolic acid (MPA):Mean apparent: Approximately 17.9 hours after oral administration and 16.6 hours after intravenous administration.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2142
Mean (+/-SD) apparent half-life and plasma clearance of MPA are 17.9 (+/-6.5) hours and 193 (+/-48) mL/min following oral administration and 16.6 (+/-5.8) hours and 177 (+/-31) mL/min following intravenous administration, respectively.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2752

8.8 Mechanism of Action

The active metabolite of mycophenolate, mycophenolic acid, prevents T-cell and B-cell proliferation and the production of cytotoxic T-cells and antibodies. Lymphocyte and monocyte adhesion to endothelial cells of blood vessels that normally part of inflammation is prevented via the glycosylation of cell adhesion molecules by MPA. MPA inhibits de novo purine biosynthesis (that promotes immune cell proliferation) by inhibiting inosine 5’-monophosphate dehydrogenase enzyme (IMPDH), with a preferential inhibition of IMPDH II. IMPDH normally transforms inosine monophosphate (IMP) to xanthine monophosphate (XMP), a metabolite contributing to the production of guanosine triphosphate (GTP). GTP is an important molecule for the synthesis of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and protein. As a result of the above cascade of effects, mycophenolate mofetil reduces de-novo production of guanosine nucleotides, interfering with the synthesis of DNA, RNA, and protein required for immune cell production. Further contributing to the above anti-inflammatory effects, MMF depletes tetrahydrobiopterin, causing the decreased function of inducible nitric oxide synthase enzyme, in turn decreasing the production of peroxynitrite, a molecule that promotes inflammation.
As a potent, selective, noncompetitive, and reversible, inhibitor of inosine monophosphate dehydrogenase (IMPDH), mycophenolic acid (MPA), the active metabolite /of mycophenolate mofetil/, inhibits the de novo synthesis pathway of guanosine nucleotides without being incorporated into DNA. Because T and B lymphocytes are critically dependent for their proliferation on de novo synthesis of purines, while other cell types can utilize salvage pathways, MPA has potent cytostatic effects on lymphocytes. MPA inhibit proliferative responses of T and B lymphocytes to both mitogenic and allospecific stimulation. The addition of guanosine or deoxyguanosine reverses the cytostatic effects of MPA on lymphocytes. MPA also suppresses antibody formation by B lymphocytes. MPA prevents the glycosylation of lymphocytes and monocyte glycoproteins that are involved in intercellular adhesion of these cells to endothelial cells, and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection. Mycophenolate mofetil dose not inhibit the early events in the activation of human peripheral blood mononuclear cells, such as the production of interleukin-1 and interleukin-2, but does block the coupling of these events to DNA synthesis and proliferation.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2141

8.9 Human Metabolite Information

8.9.1 Cellular Locations

Membrane

8.9.2 Metabolite Pathways

8.10 Biochemical Reactions

9 Use and Manufacturing

9.1 Uses

Immunosuppressive agent
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2751
MEDICATION
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. 1132
Anti-Inflammatory Agents, Non-Steroidal, Antineoplastic Agents, Dermatologic Agents, Enzyme Inhibitors, Immunosuppressive Agents
National Library of Medicine, SIS; ChemIDplus Record for Mycophenolate Mofetil (128794-94-5), MESH Heading. Available from, as of March 15, 2006: https://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp

<b>Use (kg; approx.) in Germany (2009):</b> >10000

<b>Consumption (g per capita; approx.) in Germany (2009):</b> 0.122

<b>Calculated removal (%):</b> 10.2

9.1.1 Use Classification

Human drugs -> Immunosuppressants -> Human pharmacotherapeutic group -> EMA Drug Category
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

9.2 Methods of Manufacturing

P.H. Nelson et al., US 4753935 (1988 to Syntex)
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. 1132

9.3 Formulations / Preparations

Parenteral: For injection: 500 mg (of mycophenolate mofetil), CellCept ( contains polysorbate 80), (Roche). /Mycophenolate mofetil hydrochloride/
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 3677
Oral: Capsules: 250 mg, CellCept, (Roche); For oral suspension: 200 mg/mL , CellCept ( contains aspartame), (Roche); Tablets: 500 mg, CellCept, (Roche).
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 3677

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

1 of 2
View All
Pictogram(s)
Irritant
Health Hazard
Environmental Hazard
Signal
Danger
GHS Hazard Statements

H302 (98.1%): Harmful if swallowed [Warning Acute toxicity, oral]

H341 (13.2%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]

H360 (22.6%): May damage fertility or the unborn child [Danger Reproductive toxicity]

H372 (11.3%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

H400 (88.7%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

H410 (15.1%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

Precautionary Statement Codes

P203, P260, P264, P270, P273, P280, P301+P317, P318, P319, P330, P391, P405, and P501

(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 53 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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.

10.1.2 Hazard Classes and Categories

Acute Tox. 4 (98.1%)

Muta. 2 (13.2%)

Repr. 1B (22.6%)

STOT RE 1 (11.3%)

Aquatic Acute 1 (88.7%)

Aquatic Chronic 1 (15.1%)

Acute Tox. 4 (100%)

Muta. 2 (100%)

Repr. 1B (100%)

STOT SE 1 (100%)

Aquatic Chronic 1 (100%)

10.2 Accidental Release Measures

10.2.1 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.

10.3 Regulatory Information

10.3.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl mycophenolate mofetil, 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 3, 2006: https://www.fda.gov/cder/ob/
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl mycophenolate mofetil hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Mycophenolate mofetil hydrochloride/
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 Drug Induced Liver Injury

Compound
mycophenolate mofetil
DILI Annotation
Less-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

11.1.2 Interactions

In the presence of renal impairment, acyclovir or ganciclovir may compete with mycophenolic acid glucuronide (MPAG) for tubular secretion, thus further increasing plasma concentrations of each.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2143
Potential pharmacokinetic interaction (decreased plasma concentrations of levonorgestrel). Oral contraceptives should be administered with caution in patients receiving mycophenolate mofetil and additional methods of birth control methods should be considered.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 3676
Concurrent administration /with magnesium or aluminum hydroxide containing antacids/ may result in decreased absorption of mycophenolate; simultaneous administration is not recommended.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2143
Plasma concentrations of mycophenolic acid (MPA) may be decreased as a result of interruption of enterohepatic recirculation of mycophenolic acid glucuronide (MPAG) possibly caused by intestinal binding with cholestyramine /when mycophenolate and cholestyramine are used concurrently/.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2143
For more Interactions (Complete) data for MYCOPHENOLATE MOFETIL (7 total), please visit the HSDB record page.

11.1.3 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

11.1.4 Human Toxicity Excerpts

/CASE REPORTS/ Mycophenolate mofetil (MMF) is one of the new immunosuppressive drugs used in renal transplantation. MMF inhibits the de novo purine synthesis. Since this purine synthesis in lymphocytes entirely depends on the de novo pathway, MMF is considered to cause a selective inhibition of T- and B lymphocytes. Recently, 4 transplant patients out of 30 developed a severe anemia in the early post-transplantation period. Their immediate post-transplantation immunosuppression consisted of corticosteroids, cyclosporine and MMF. They all received anti-T-lymphocyte globulin (ATG) as induction treatment or because of rejection. In all 4 patients, iron supplementation and a treatment with erythropoietin were started. Blood loss, deficiencies, hemolysis, drug interactions or viral infections were excluded as causes of the anemia. Bone marrow biopsies were carried out, showing pure red cell aplasia that was ascribed to the use of MMF. Cessation or reduction of MMF was followed by a hematological improvement after 5-9 days. We hypothesized that MMF has a broader antiproliferative effect than its proposed lymphocyte-specific effect.
Engelen W et al; Clin Nephrol. 2003 60(2):119-24.

11.1.5 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ In acute oral toxicity studies, no deaths occurred in adult mice at doses up to 4000 mg/kg or in adult monkeys at doses up to 1000 mg/kg; these were the highest doses of mycophenolate mofetil tested in these species. These doses represent 11 times the recommended clinical dose in renal transplant patients and approximately 7 times the recommended clinical dose in cardiac transplant patients when corrected for BSA.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2758
/LABORATORY ANIMALS: Acute Exposure/ In adult rats, deaths occurred after single-oral doses of 500 mg/kg of mycophenolate mofetil. The dose represents approximately 3 times the recommended clinical dose in cardiac transplant patients when corrected for BSA.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2758
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ A study in female rats at oral doses of 4.5 mg/kg a day found that mycophenolate caused malformations (primarily of the head and eyes) in the first generation offspring in the absence of maternal toxicity. Studies in rats and rabbits at oral doses of 6 mg/kg a day and 90 mg/kg a day, respectively, fond fetal resorptions and malformations in the absence of maternal toxicity.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2143
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Studies in male rats at oral doses of up to 20 mg/kg a day found no effect on fertility. A study in female rats at oral doses of 4.5 mg/kg a day found no effect on fertility or reproductive parameters in the dams or in the offspring.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2142
/GENOTOXICITY/ No evidence of genotoxicity, with or without metabolic activation, was found in the bacterial mutation assay, the yeast mitotic gene conversion assay, the mouse micronucleus aberration assay, or the Chinese hamster ovary cell (CHO) chromosomal aberration assay.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2143

11.1.6 Populations at Special Risk

Because mycophenolate mofetil inhibits inosine monophosphate dehydrogenase, the drug should be avoided, on theoretical grounds, in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), including Kelley-Seegmiller or Lesch-Nyhan syndrome.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 3676
CellCept Oral Suspension contains aspartame, a source of phenylalanine (0.56 mg phenylalanine/mL suspension). Therefore, care should be taken if CellCept Oral Suspension is administered to patients with phenylketonuria.
Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2755

11.1.7 Protein Binding

The protein binding of mycophenolic acid, the metabolite of mycophenolate mofetil, is 97% and it is mainly bound to albumin. MPAG, the inactive metabolite, is 82% bound to plasma albumin at normal therapeutic concentrations. At elevated MPAG concentrations due to various reasons, including renal impairment, the binding of MPA may be decreased due to competition for binding.

11.2 Ecological Information

11.2.1 Environmental Fate / Exposure Summary

Mycophenolate mofetil's production and use as an immunosuppressive agent may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.9X10-13 mm Hg at 25 °C indicates mycophenolate mofetil will exist solely in the particulate phase in the atmosphere. Particulate-phase mycophenolate mofetil will be removed from the atmosphere by wet or dry deposition. Mycophenolate mofetil 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, mycophenolate mofetil is expected to have moderate mobility based upon an estimated Koc of 470. Measured pKa values for mycophenolate mofetil are 5.6 (tertiary amine) and 8.5 (phenol), indicating that this compound will exist partially in the anion form under basic conditions and partially in the cation form under acidic conditions in the environment. Volatilization from moist soil surfaces is not expected to be an important fate process because ionic compounds do not volatilize and based upon an estimated Henry's Law constant of 5.5X10-15 atm-cu m/mole for the neutral species. Mycophenolate mofetil is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data were not available. If released into water, mycophenolate mofetil is expected to adsorb very little to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process because ionic compounds do not volatilize and based upon this compound's estimated Henry's Law constant for the neutral species. An estimated BCF of 38 suggests the potential for bioconcentration in aquatic organisms is moderate. A base-catalyzed second-order hydrolysis rate constant of 0.14 L/mole-sec was estimated using a structure estimation method; this corresponds to half-lives of 1.6 years and 59 days at pH values of 7 and 8, respectively. Occupational exposure to mycophenolate mofetil may occur through inhalation and dermal contact with this compound at workplaces where mycophenolate mofetil is produced or used. Exposure to mycophenolate mofetil among the general population may be limited to those administered this substance as a drug. (SRC)

11.2.2 Artificial Pollution Sources

Mycophenolate mofetil's production and use as an immunosuppressive agent(1) may result in its release to the environment through various waste streams(SRC).
(1) Physicians Desk Reference. 60th ed. Thomson PDR. Montvale, NJ p.2751 (2006)

11.2.3 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 470(SRC), determined from a log Kow of 2.4(2) and a regression-derived equation(3), indicates that mycophenolate mofetil is expected to have moderate mobility in soil(SRC). Measured pKa values for mycophenolate mofetil are 5.6 (tertiary amine) and 8.5 (phenol)(4), indicating that this compound will exist partially in the anion form under basic conditions and partially in the cation form under acidic conditions in the environment. Volatilization of mycophenolate mofetil from moist soil surfaces is not expected to be an important fate process(SRC) because ionic compounds do not volatilize and based on an estimated Henry's Law constant of 5.5X10-15 atm-cu m/mole for the neutral species(SRC), calculated using a fragment constant estimation method(5). Mycophenolate mofetil is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.9X10-13 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) O'Neil MJ ed; The Merck Index. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc. p 1132 (2001)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990)
(4) Physicians Desk Reference. 60th ed. Thomson PDR. Montvale, NJ p.2751 (2006)
(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 470(SRC), determined from a log Kow of 2.4(2) and a regression-derived equation(3), indicates that mycophenolate mofetil is expected to adsorb very little to suspended solids and sediment(SRC). Measured pKa values for mycophenolate mofetil are 5.6 (tertiary amine) and 8.5 (phenol)(4), indicating that this compound will exist partially in the anion form under basic conditions and partially in the cation form under acidic conditions in the environment. Volatilization from water surfaces is not expected(3) becuase ionic compounds do not volatilize and based upon an estimated Henry's Law constant of 5.5X10-15 atm-cu m/mole for the neutral species(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 38(SRC), from a log Kow of 2.4(2), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). A base-catalyzed second-order hydrolysis rate constant of 0.14 L/mole-sec(SRC) was estimated using a structure estimation method(7); this corresponds to half-lives of 1.6 years and 59 days at pH values of 7 and 8, respectively. Biodegradation data were not available(SRC, 2006).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) O'Neil MJ ed; The Merck Index. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc. p 1132 (2001)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990)
(4) Physicians Desk Reference. 60th ed. Thomson PDR. Montvale, NJ p.2751 (2006)
(5) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(6) Franke C et al; Chemosphere 29: 1501-14 (1994)
(7) 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)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), mycophenolate mofetil, which has an estimated vapor pressure of 1.9X10-13 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 mycophenolate mofetil may be removed from the air by wet or dry deposition(SRC). Mycophenolate mofetil 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 0.14 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 1.6 years and 59 days at pH values of 7 and 8, respectively(1). Mycophenolate mofetil 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 38 was calculated for mycophenolate mofetil(SRC), using a measured log Kow of 2.4(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).
(1) O'Neil MJ ed; The Merck Index. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc. p 1132 (2001)
(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

The Koc of mycophenolate mofetil is estimated as 470(SRC), using a log Kow of 2.4(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that mycophenolate mofetil is expected to have moderate mobility in soil. Measured pKa values for mycophenolate mofetil are 5.6 (tertiary amine) and 8.5 (phenol)(4), indicating that this compound will exist partially in the anion form under basic conditions and partially in the cation form under acidic conditions in the environment.
(1) O'Neil MJ ed; The Merck Index. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc. p 1132 (2001)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9 (1990)
(3) Swann RL et al; Res Rev 85: 17-28 (1983)
(4) Physicians Desk Reference. 60th ed. Thomson PDR. Montvale, NJ p.2751 (2006)

11.2.7 Volatilization from Water / Soil

The Henry's Law constant for mycophenolate mofetil is estimated as 5.5X10-15 atm-cu m/mole(SRC) using a fragment constant estimation method(1). Measured pKa values for mycophenolate mofetil are 5.6 (tertiary amine) and 8.5 (phenol)(2), indicating that this compound will exist partially in the anion form under basic conditions and partially in the cation form under acidic conditions in the environment. Based on this Henry's Law constant and the fact that ionic compounds do not volatilize, mycophenolate mofetil is expected to be essentially nonvolatile from moist soil or water surfaces(3). Mycophenolate mofetil is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.9X10-13 mm Hg(SRC), determined from a fragment constant method(4).
(1) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(2) Physicians Desk Reference. 60th ed. Thomson PDR. Montvale, NJ p.2751 (2006)
(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 mycophenolate mofetil 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 mycophenolate is distributed into breast milk in humans. However, studies in rats treated with mycophenolate have shown mycophenolic acid (MPA) to be distributed into milk.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006., p. 2142

11.2.10 Probable Routes of Human Exposure

Occupational exposure to mycophenolate mofetil may occur through inhalation and dermal contact with this compound at workplaces where mycophenolate mofetil is produced or used. Exposure to mycophenolate mofetil 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 Chemical Co-Occurrences in Literature

13.6 Chemical-Gene Co-Occurrences in Literature

13.7 Chemical-Disease Co-Occurrences in Literature

14 Patents

14.1 Depositor-Supplied Patent Identifiers

14.2 WIPO PATENTSCOPE

14.3 FDA Orange Book Patents

14.4 Chemical Co-Occurrences in Patents

14.5 Chemical-Disease Co-Occurrences in Patents

14.6 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

  • Avoid multivalent ions. Take multivalent ions such as calcium, iron, or magnesium at least 2 hours after taking this medication.
  • Take on an empty stomach. Take at least 1 hour before or 2 hours after meals.

15.4 Pathways

16 Biological Test Results

16.1 BioAssay Results

17 Classification

17.1 MeSH Tree

17.2 NCI Thesaurus Tree

17.3 ChEBI Ontology

17.4 KEGG: Drug

17.5 KEGG: USP

17.6 KEGG: ATC

17.7 KEGG: Target-based Classification of Drugs

17.8 ChemIDplus

17.9 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

17.10 ChEMBL Target Tree

17.11 UN GHS Classification

17.12 NORMAN Suspect List Exchange Classification

17.13 CCSBase Classification

17.14 EPA DSSTox Classification

17.15 FDA Drug Type and Pharmacologic Classification

17.16 MolGenie Organic Chemistry Ontology

18 Information Sources

  1. CAS Common Chemistry
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    https://creativecommons.org/licenses/by-nc/4.0/
  2. ChemIDplus
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    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
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    https://comptox.epa.gov/dashboard/chemical-lists/
  6. European Chemicals Agency (ECHA)
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    https://echa.europa.eu/web/guest/legal-notice
    2-(morpholin-4-yl)ethyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate
    https://echa.europa.eu/substance-information/-/substanceinfo/100.155.374
    2-(morpholin-4-yl)ethyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate (EC: 627-027-6)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/159976
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  8. Hazardous Substances Data Bank (HSDB)
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    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  14. 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
  15. 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
  16. 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/
  17. The Cambridge Structural Database
  18. DailyMed
  19. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  20. IUPHAR/BPS Guide to PHARMACOLOGY
    LICENSE
    The Guide to PHARMACOLOGY database is licensed under the Open Data Commons Open Database License (ODbL) https://opendatacommons.org/licenses/odbl/. Its contents are licensed under a Creative Commons Attribution-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-sa/4.0/)
    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  21. Therapeutic Target Database (TTD)
  22. 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
  23. 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
  24. Drugs@FDA
    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
  25. EU Clinical Trials Register
  26. FDA Orange Book
    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
  27. FDA Medication Guides
    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
  28. 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/
    MYCOPHENOLATE MOFETIL
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  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
    Therapeutic category of drugs in Japan
    http://www.genome.jp/kegg-bin/get_htext?br08301.keg
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
  31. 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
  32. Metabolomics Workbench
  33. 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
  34. NIPH Clinical Trials Search of Japan
  35. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  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. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  38. SpectraBase
  39. Springer Nature
  40. 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/
  41. Wikidata
  42. 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
  43. PubChem
  44. GHS Classification (UNECE)
  45. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  46. PATENTSCOPE (WIPO)
  47. NCBI
CONTENTS