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

Short Communication
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Abstract

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.

Keywords

Lenalidomide Cytochrome P450 CYP inhibition CYP induction Drug–drug interactions 
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Notes

Acknowledgments

Authors would like to thank Rebecca R. Campbell of Xenotech LLC, and Anthony Glazer of Covance Laboratories Inc., for their contributions.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Early Drug Development, Celgene CorporationSummitUSA

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