Sex-related differences in drug disposition in man

Sex-related differences in the disposition of some analgesics, anxiolytics and hypnotics have recently been reported. With certain benzodiazepines, sex has been shown to be a more important determinant of variability in drug disposition than age, while with other benzodiazepines an age-related decline in clearance was more pronounced in men than women. In young healthy adults these sex-related differences in drug disposition were related to the phase of the menstrual cycle, oral contraceptive steroid administration, and variations in plasma concentrations of albumin, alpha 1-acid glycoprotein, free fatty acids and sex hormones. While none of the sex-related differences so far reported necessitates the modification of a therapeutic dosage regimen, it is prudent that future protocols for pharmacokinetic studies should regard age, sex, the menstrual cycle and oral contraceptive steroids as potential sources of variability.