PURPOSE: To establish the cytochrome P450 (CYP) isozymes involved in the metabolism of the alkylating agent, thiotepa, to the pharmacologically active metabolite, @entity29890 . METHODS: In vitro chemical inhibition studies were conducted by incubating thiotepa and pooled @entity1 hepatic microsomes in the presence of known inhibitors to @entity4914 , @entity5944 , @entity12327 , @entity5060 , @entity4433 , @entity5320 , @entity5321 , and @entity5322 . Studies were also performed with cloned, expressed @entity5322 , @entity5944 , @entity5321 and @entity11670 microsomes, and anti- @entity11670 monoclonal antibody. RESULTS: Known @entity5322 inhibitors reduced @entity29890 production. Inhibition with @entity5321 inhibitors was inconsistent. All other inhibitors produced little or no change in @entity29890 formation. Cloned, expressed @entity11670 and @entity5322 microsomes catalyzed @entity29890 formation, whereas @entity5944 and @entity5321 did not. Incubation of thiotepa with anti- @entity11670 antibody and cloned, expressed @entity11670 microsomes resulted in reductions in the formation of @entity29890 , but no change in @entity29890 formation occurred in @entity1 liver microsomes. CONCLUSIONS: Thiotepa is metabolized in @entity1 liver microsomes by @entity5322 (major) and @entity11670 (minor). There is a potential for CYP-mediated drug interactions with thiotepa. Pharmacokinetic variability of thiotepa may be related to expression of hepatic CYP isozymes.

Cytochrome P450 isozymes 3A4 and 2B6 are involved in the in vitro @entity1 metabolism of thiotepa to XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity11670 :: ('1555', 'Gene') :: ['CYP2B6'] @entity29890 :: ('MESH:D013721', 'Chemical') :: ['TEPA'] @entity5944 :: ('1548', 'Gene') :: ['CYP2A6'] @entity5320 :: ('1565', 'Gene') :: ['CYP2D6'] @entity4433 :: ('1557', 'Gene') :: ['CYP2C19'] @entity5322 :: ('1576', 'Gene') :: ['CYP3A4'] @entity5060 :: ('1559', 'Gene') :: ['CYP2C9'] @entity12327 :: ('1558', 'Gene') :: ['CYP2C8'] @entity4914 :: ('1544', 'Gene') :: ['CYP1A2'] @entity5321 :: ('1571', 'Gene') :: ['CYP2E1']
@entity29890 :: (MESH:D013721,Chemical) :: ['TEPA']
