Effects of Sex and Fed State Differences on the Pharmacokinetics of Drugs in Humans

Sex and fed state are critical factors influencing drug pharmacokinetics, potentially affecting efficacy and safety. This study evaluates the impact of sex and food intake on key pharmacokinetics parameters-maximum plasma concentration, time to maximum plasma concentration, area under the curve to last time point, area under the curve extrapolated to infinity, and elimination half-life-for amlodipine, dapagliflozin, empagliflozin, rivaroxaban, deferiprone, deflazacort, and siponimod.

Pooled data from clinical studies were analyzed. Geometric mean values and coefficients of variation were calculated for men and women. Statistical comparisons were performed using appropriate tests to derive p-values for sex (men vs women) and fed state (fasting vs fed) differences.

Significant sex-based differences were observed. Women exhibited significantly higher systemic exposure (the maximum plasma concentration and area under the curve) for amlodipine, dapagliflozin, empagliflozin, rivaroxaban (in the fed state and overall), deferiprone (overall and fed), and siponimod (overall and fasting). The time to the maximum plasma concentration was significantly faster for deflazacort in women. Fed state comparisons showed that food significantly increased the time to the maximum plasma concentration for deferiprone in both sexes and rivaroxaban in women, while decreasing the maximum plasma concentration for rivaroxaban in both sexes.

Sex and fed state significantly influence the pharmacokinetics of several drugs. These findings underscore the necessity of considering these factors in clinical dosing regimens and drug development to optimize therapeutic outcomes.