Metabolite Profiles of Bazedoxifene in Mice, Rats and Monkeys (original) (raw)

Abstract

Bazedoxifene (BZA) is a selective estrogen receptor modulator that is being developed for the prevention and treatment of postmenopausal osteoporosis. Metabolite profiles of [14C]BZA were investigated in mouse, rat and monkey liver microsomes, as well as in mice, rats and monkeys following a single oral administration of [14C]BZA. In vitro incubations with 50 µM [14C]BZA in the presence of mouse liver microsomes and NADPH produced BZA-N-oxide. CYP450 mediated metabolism of BZA was negligible in rat and monkey liver microsomes. When UDPGA was included in the incubations, BZA was extensively metabolized in all species examined. BZA-4'-glucuronide and BZA-5-glucuronide were observed in all species, while BZA-N-oxide, BZA-4'-glucuronide N-oxide, and BZA-5-glucuronide N-oxide were also generated in mouse liver microsomes. Mouse liver microsomes generated a 2-fold greater amount of the 4'-glucuronide than the 5-glucuronide. Rat liver microsomes generated a 3-fold greater amoun...

William DEMAIO hasn't uploaded this paper.

Let William know you want this paper to be uploaded.

Ask for this paper to be uploaded.