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- W2410068056 abstract "Medroxyprogesterone acetate (MPA) is one of the most frequently prescribed progestin for clinical conception, hormone replacement therapy, and adjuvant endocrine therapy. MPA has a low oral bioavailability due to extensive metabolism. However, MPA metabolism was poorly documented. This study was intended to profile the phase I metabolites of MPA and the P450 isoforms involved. After MPA was incubated with human liver microsomes and NADPH-generating system, five main metabolites (namely M-1, M-2, M-3, M-4, and M-5) were isolated by HPLC. Three major metabolites (M-2, M-4 and M-3) were tentatively identified to be 6β-, 2β-, and 1β- hydroxy MPA by LC/MS and 1HNMR. By consecutive metabolism of purified M-2, M-3 and M-4, M-1 and M-5 were proposed to be 2β-, 6β-dihydroxy MPA and 1-dehydro MPA, respectively. CYP3A4 was identified to be the isoform primarily involved in the formation of M-2 to M-5 in studies using specific inhibitors, recombinant P450s, and correlation comparisons. Rat and minipig liver microsomes were included to evaluate species differences, and the results showed little difference among the species. In conclusion, CYP3A4 was the major CYP isoform involved in MPA hydroxylation, with 6β-, 2β-, and 1β- being the preferred hydroxylation sites. Minipig and rat could be the surrogate models for man in MPA pharmacokinetic /script>" @default.
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- W2410068056 date "2008-05-11" @default.
- W2410068056 modified "2023-09-23" @default.
- W2410068056 title "Metabolic profiling and P450 phenotyping of medroxyprogesterone acetate" @default.
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