Introduction: Pharmacological research has traditionally been skewed toward male subjects, leading to uniform treatment guidelines for both men and women that assume similar drug pharmacokinetics across sexes. This oversight contributes to women experiencing adverse drug reactions on average twice as often as men. More recent studies have revealed significant pharmacokinetic differences between the sexes, partly due to different sex hormone levels. Additionally, intraindividual differences in women have been observed due to fluctuating estrogen levels, impacting important aspects of drug pharmacokinetics.
Areas covered: This review highlights key sex differences in drug pharmacokinetics, focusing on absorption, distribution, metabolism, and excretion. A particular emphasis is placed on the role of cytochrome P450 (CYP) and uridine diphosphate-glucuronosyltransferase (UGT) enzymes in drug metabolism, and on the role of P-glycoprotein (P-gp). The impact of estrogens is reviewed by exploring how drug pharmacokinetics change over the menstrual cycle, before and after menopause, and with estrogen-containing medications.
Expert opinion: Personalized dosing based on sex and estrogen levels is important for improving treatment outcomes in female drug users. Clinical trials of drugs likely affected by these factors should incorporate pharmacokinetic studies that distinguish between sexes and evaluate the impact of estrogens, aiming to develop optimized dosing regimens.
Keywords: CYP enzymes; drug pharmacokinetics; estrogens; hormone replacement therapy; menopause; menstrual cycle; oral contraceptives; sex differences.