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 XXXX metabolism of thiotepa to @entity29890 .

@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']
@entity1 :: (9606,Species) :: ['human']
