Drug interactions of thalidomide with midazolam and cyclosporine A: heterotropic cooperativity of human cytochrome P450 3A5.

ABSTRACT: There is growing clinical interest of thalidomide because of its immunomodulatory and antiangiogenic properties, despite its teratogenicity. However, little information about thalidomide has been reported regarding its precise effects on drug-metabolizing enzymes. We investigated the effects of thalidomide on cytochrome P450 (P450) enzymes in human liver microsomes to clarify the potential for possible drug interactions. Thalidomide inhibited S-mephenytoin 4'-hydroxylation activities of recombinant P450 2C19 and human liver microsomes: the apparent concentration of thalidomide producing 50% inhibition was approximately 270 microM for P450 2C19. Midazolam 4-hydroxylation activities were suppressed by thalidomide, but activities of 1'-hydroxylation and total midazolam oxidation and testoster

SUBMITTER: Okada Y 

PROVIDER: S-EPMC2719675 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature