Lenalidomide: in vitro evaluation of the metabolism and assessment of cytochrome P450 inhibition and induction

Purpose To assess the potential for drug-drug interactions between lenalidomide and substrates and inhibitors of cytochrome P450 (CYP) isozymes. Methods In vitro metabolism of lenalidomide by human liver microsomes, recombinant human CYPs and human hepatocytes was evaluated. The inhibitory and induc...

Full description

Saved in:
Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 2009-05, Vol.63 (6), p.1171-1175
Main Authors: Kumar, Gondi, Lau, Henry, Laskin, Oscar
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cancer Research
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System - biosynthesis
Cytochrome P-450 Enzyme System - metabolism
Hepatocytes - enzymology
Humans
In Vitro Techniques
Isoenzymes
Medical sciences
Medicine
Medicine & Public Health
Microsomes, Liver - enzymology
Oncology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Recombinant Proteins - metabolism
Short Communication
Substrate Specificity
Thalidomide - analogs & derivatives
Thalidomide - metabolism
Thalidomide - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Purpose To assess the potential for drug-drug interactions between lenalidomide and substrates and inhibitors of cytochrome P450 (CYP) isozymes. Methods In vitro metabolism of lenalidomide by human liver microsomes, recombinant human CYPs and human hepatocytes was evaluated. The inhibitory and inductive effects of lenalidomide on the CYP activities were evaluated in human liver microsomes and cultured human hepatocytes, respectively. Results In vitro incubation of lenalidomide with human liver microsomes, recombinant-CYP isozymes, and human hepatocytes did not result in Phase I or Phase II metabolism, confirming the low propensity of lenalidomide for metabolism in vivo in humans. In vitro, lenalidomide did not inhibit CYP isozymes in human liver microsomes and did not induce CYP activities in cultured human hepatocytes. Conclusions Lenalidomide is not a substrate, inhibitor, or inducer of CYP group of enzymes; clinically relevant pharmacokinetic drug-drug interactions are unlikely to occur between lenalidomide and co-administered CYP substrates or inhibitors.
ISSN:0344-5704
1432-0843
DOI:10.1007/s00280-008-0867-7