Summary of Studies Showing Sex-Differences in Pharmacokinetics:
Bladder Anticholinergics
Oxybutynin is the prototype bladder anticholinergic. Oxybutynin is
metabolized by CYP3A4 to N-desmethyloxybutynin, which is considered to
cause many of the adverse events related to oxybutynin treatment.
Increased CYP3A4 activity and slowed renal elimination in women may
increase exposure to the metabolite and increase the likelihood of
adverse drug effects. However, an older study of oxybutynin
pharmacokinetics failed to show sex differences in the pharmacokinetics
of oxybutynin or its metabolite96.
Two randomized double-blind placebo-controlled trials assessed the
effects of age, sex and race on the pharmacokinetics, pharmacodynamics
and safety profiles of fesoterodine in 32 healthy males aged 18-45 years
and 16 young men, 16 older men and 16 older women (table 2). Total
plasma clearance of fesoterodine was highest in young men and lowest in
older women but there were no apparent sex differences in
CMax, AUC0-∞, or tmax.
Interestingly five hours after the dose was given, older women
experienced a one gram decrease in salivary volume whereas older men did
not, which provided some evidence that women are more likely to
experience adverse effects (e.g. dry mouth) from anticholinergic
medication use97. Similarly, in a study of 337
individuals darifenacin clearance was about 30% lower in
females98. No sex differences in pharmacokinetics have
been identified for solifenacin99 or
tolterodine97. Trospium demonstrates an unexplained
prolonged t1/2 in women compared to
men100. This demonstrates the complex influence of sex
on pharmacokinetics of bladder anticholinergics which are frequently
used by older adults.