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Landry K. Kamdem; Yong Liu; Vered Stearns; Susan A. Kadlubar; Jacqueline Ramirez; Stacie Jeter; Karineh Shahverdi; Bryan A. Ward; Evan Ogburn; Mark J. Ratain; et al. (Profiled Authors: Zeruesenay Desta; David A. Flockhart)
British Journal of Clinical Pharmacology. 2010;70(6):854-869.Abstract
AIMS: Little information is available regarding the metabolic routes of anastrozole and the specific enzymes involved. We characterized anastrozole oxidative and conjugation metabolism in vitro and in vivo. METHODS: A sensitive LC-MS/MS method was developed to measure anastrozole and its metabolites in vitro and in vivo. Anastrozole metabolism was characterized using human liver microsomes (HLMs), expressed cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs). RESULTS: Hydroxyanastrozole and anastrozole glucuronide were identified as the main oxidative and conjugated metabolites of anastrozole in vitro, respectively. Formation of hydroxyanastrozole from anastrozole was markedly inhibited by CYP3A selective chemical inhibitors (by >90%) and significantly correlated with CYP3A activity in a panel of HLMs (r= 0.96, P= 0.0005) and mainly catalyzed by expressed CYP3A4 and CYP3A5. The K
PMID: 21175441 PMCID: PMC3014069
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