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.