Bosch E L, Sommer I E C, Touw D J
Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands.
Department of Psychiatry and Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Expert Opin Drug Metab Toxicol. 2025 Jun;21(6):637-647. doi: 10.1080/17425255.2025.2481891. Epub 2025 Mar 20.
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.
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.
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.
传统上，药理学研究偏向于男性受试者，导致针对男性和女性的统一治疗指南，假定不同性别的药物药代动力学相似。这种疏忽导致女性平均出现药物不良反应的频率是男性的两倍。最近的研究表明，不同性别之间存在显著的药代动力学差异，部分原因是性激素水平不同。此外，由于雌激素水平波动，女性个体内差异也已被观察到，这影响了药物药代动力学的重要方面。
本综述强调了药物药代动力学中的关键性别差异，重点关注吸收、分布、代谢和排泄。特别强调了细胞色素P450（CYP）和尿苷二磷酸葡萄糖醛酸转移酶（UGT）在药物代谢中的作用，以及P-糖蛋白（P-gp）的作用。通过探讨药物药代动力学在月经周期、绝经前后以及使用含雌激素药物时如何变化，来综述雌激素的影响。
基于性别和雌激素水平的个性化给药对于改善女性药物使用者的治疗效果很重要。可能受这些因素影响的药物的临床试验应纳入区分性别的药代动力学研究，并评估雌激素的影响，旨在制定优化的给药方案。
