Sex Differences in Pharmacokinetics and Pharmacodynamics

The importance of reviewing and studying sex-based differences in pharmacologic parameters is demonstrated by the increasing data on gender variation in drug efficacy and toxicity profiles. Sex-based differences in the four major factors that contribute to interindividual pharmacokinetic variability--bioavailability, distribution, metabolism, and elimination--are theorized to stem from variations between men and women in factors such as body weight, plasma volume, gastric emptying time, plasma protein levels, cytochrome P450 activity, drug transporter function, and excretion activity. Sex-determined variations in pharmacodynamics have traditionally been more difficult to study, but a number of recent studies have explored these differences. This review examines the biologic basis of differences in pharmacokinetics and pharmacodynamics between the sexes and summarizes studies that have addressed these differences. As an example, sex-based variation in the efficacy and toxicity of antiretroviral therapy in human immunodeficiency virus (HIV)-infected patients is explored more thoroughly to illustrate some of the factors underlying sex-based differences in drug therapy.