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- W2015570731 abstract "Summary Aim : To assess the pharmacokinetics of alosetron, its effect on in vivo enzyme activities, and influence of demographic factors during repeated dosing. Methods : Thirty healthy men and women received 1 mg oral alosetron twice‐daily for 29.5 days and a single oral dose of a metabolic probe cocktail before and on the last day of alosetron dosing. Serum alosetron concentrations were measured on days 1, 8, 15, 22 and 29. Probe‐substrate and metabolite concentrations were measured after each cocktail dose. Results : Alosetron accumulation in serum was negligible. Exposure to alosetron did not alter probe‐metabolite/substrate ratios associated with CYP2C19, 2E1, 2C9, or 3A4 activity, but modestly decreased those associated with CYP1A2 and N ‐acetyltransferase activity. Systemic exposure to alosetron was higher in women, positively correlated with age and body mass index, and negatively correlated with CYP1A2 activity. Incidence of constipation was higher in women, but not associated with alosetron concentration. Conclusions : Single dose data can reliably predict the pharmacokinetics of alosetron after repeated doses. Alosetron exhibits limited potential for inhibition of cytochrome P450‐mediated metabolism. Interindividual differences in alosetron pharmacokinetics associated with demographic factors may be related to strong dependence on metabolism by CYP1A2." @default.
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- W2015570731 date "2004-06-25" @default.
- W2015570731 modified "2023-10-14" @default.
- W2015570731 title "Alosetron repeat dose pharmacokinetics, effects on enzyme activities, and influence of demographic factors" @default.
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- W2015570731 doi "https://doi.org/10.1111/j.1365-2036.2004.02031.x" @default.
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