Effect of sex on the renal elimination of anticholinergic medications
Kidney function is integral to drug elimination. Glomerular filtration is related to body mass. Males typically have a greater body weight than females45, so generally glomerular filtration is greater in males than females. This likely explains the majority of sex-differences in renal drug clearance, though this has not been observed for all drugs. Sex has been found to be a significant factor in methotrexate clearance, with a 17% reduction in females after standardizing doses for body weight70. Some authors have reasoned that for narrow therapeutic index drugs the sex-related effect on kidney function may be clinically relevant70,71. Pharmacokinetic studies have confirmed sex-differences in renal clearance for many drugs including the weakly anticholinergic drug digoxin, which has slower clearance in females72 and the moderately anticholinergic drug amantadine, which has been shown to have significantly higher renal clearance in men due to putative sex differences in renal tubule secretion by organic cation transporters73.
Summary of Studies Showing Sex-Differences in Pharmacokinetics: