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Sex and age differences in the pharmacokinetics of alosetron
K M Koch1, J L Palmer, N Noordin
1Clinical Pharmacology, GlaxoSmithKline, North Carolina, USA.
Aims:
To determine the effects of sex and age on the pharmacokinetics of alosetron.
Methods:
Single oral and intravenous 2 mg doses of alosetron were administered on separate occasions to 48 healthy, young and elderly, males and females. Serum was sampled for 12 h post-dose to measure alosetron concentrations.
Results:
Serum concentrations of alosetron were higher in females than in males, resulting from a sex difference in clearance by metabolism. Mean clearance values were 504 vs 677 ml min(-1) in young females vs males (mean ratio 0.75), and 461 vs 670 ml min(-1) in elderly females vs males (mean ratio 0.69). The sex difference in alosetron pharmacokinetics achieved statistical significance in the elderly, but not in the young. Irrespective of sex, alosetron clearance was increased by smoking. Serum concentrations tended to be higher in the elderly, although the effect of age was generally not significant. Volume of distribution was smaller in females (approximately 63 l) compared with males (approximately 84 l), regardless of age or the sex difference in body weight.
Conclusions:
A significant difference in clearance by metabolism of alosetron between the sexes, and possibly between the young and elderly was observed.