Sex and racial differences in pharmacological response: where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics.

The Food and Drug Administration (FDA) reviewed 300 new drug applications between 1995 and 2000. Of the 163 that included a sex analysis, 11 drugs showed a >40% difference in pharmacokinetics between males and females, which was listed on the product label, yet no dosing recommendations were made based on sex. Female sex has been shown to be a risk factor for clinically relevant adverse drug reactions. Would simply dosing females based on their different pharmacokinetics decrease the incidence of adverse events? The answer is not known. Sex-dependent pharmacodynamic effects have been identified. The role of pharmacokinetics vs. pharmacodynamics is unclear, as is the impact of pharmacogenetics on both. This review highlights a few specific examples in each area in which sex differences in pharmacokinetics and pharmacodynamics are important and provides recommendations for additional needed research.