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- W2055637124 abstract "The pharmacokinetics of cilostazol was investigated after oral and intravenous administration in both male and female rats. After oral administration, area under serum concentration-time curve (AUC) was about 35-fold higher in female rats than in male rats, and absolute bioavailability was about 5.8-fold higher in female rats than in male rats. Total body clearance (CL(total)) for female rats was around one-sixth of that for male rats. In vivo hepatic clearance (CL(h)) calculated based on isolated liver perfusion studies was even higher than or around 90% of the in vivo CL(total) of cilostazol for female and male rats, respectively, indicating that cilostazol is mainly eliminated by the liver in both male and female rats. In vitro metabolism studies utilizing hepatic microsomes and recombinant cytochrome (CYP) isoforms clearly indicated that major metabolites of cilostazol were generated extensively with hepatic microsomes of male rats and that male-predominant CYP3A2 and male-specific CYP2C11 were mainly responsible for the hepatic metabolism of cilostazol. Therefore, the great sex differences in the pharmacokinetics of cilostazol were mainly attributed to the large difference in hepatic metabolism. Our experimental results also suggested that the substantial metabolism of cilostazol in the small intestine and its possible saturation would be responsible for dose-dependent bioavailability in both male and female rats." @default.
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- W2055637124 date "2011-07-01" @default.
- W2055637124 modified "2023-09-27" @default.
- W2055637124 title "Sex differences in pharmacokinetics of cilostazol in rats" @default.
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- W2055637124 doi "https://doi.org/10.3109/00498254.2011.590242" @default.
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