Lenalidomide: in vitro evaluation of the metabolism and assessment of cytochrome P450 inhibition and induction.
OBJECTIVE
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.
Kumar
Gondi
G
Early Drug Development, Celgene Corporation, Summit, NJ 07901, USA. gkumar@celgene.com
Lau
Henry
H
Laskin
Oscar
O
D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D022781:Hepatocytes / Q000201:enzymology*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes; D000077269:Lenalidomide; D008862:Microsomes, Liver / Q000201:enzymology*; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000970:Antineoplastic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D011994:Recombinant Proteins; D013792:Thalidomide; D003577:Cytochrome P-450 Enzyme System; D000077269:Lenalidomide