Sex Differences in Pharmacokinetics.

Abstract

Because women have been excluded from most clinical trials, assessment of sex differences in pharmacokinetics is available for a minority of currently prescribed drugs. In a 2020 analysis, substantial pharmacokinetic (PK) sex differences were established for 86 drugs: women given the same drug dose as men routinely generated higher blood concentrations and longer drug elimination times than men. 96% of drugs with higher PK values in women were associated with a higher incidence of adverse drug reactions (ADRs) in women than men; in the small number of instances when PKs of men exceeded those of women, this sex difference positively predicted male-biased ADRs in only 29% of cases. The absence of sex-stratified PK information for many medications raises the concern that sex differences in pharmacokinetics may be widespread and of clinical significance, contributing to sex-specific patterns of ADRs. Administering equal drug doses to women and men neglects sex differences in pharmacokinetics and body weight, risks overmedication of women, and contributes to female-biased ADRs. Evidence-based dosing adjustments are recommended to counteract this sex bias.