Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland.
University of Basel, Basel, Switzerland.
Eur Geriatr Med. 2022 Jun;13(3):559-565. doi: 10.1007/s41999-021-00587-0. Epub 2021 Nov 19.
The proportion of women increases with advanced age, but older women are often underrepresented in clinical trials. Therefore, little is known about the combined effect of sex- and age-related physiological changes on drug pharmacokinetics.
We compiled clinical studies, which investigated sex-related pharmacokinetic differences both in older and young women and men. The ratio women/men was calculated for various pharmacokinetic parameters across adulthood to assess sex-related differences in drug pharmacokinetics with aging. The contribution of body weight and drug characteristics to sex-related pharmacokinetic differences were explored using analysis of variance.
We found 67 studies reporting the pharmacokinetics for 56 drugs both in older and young women and men. Median peak concentration (C) (interquartile range (IQR)) and drug exposure (AUC) (IQR) were 22% (8-41%) and 20% (0-39%) higher in women compared with men whereas time to peak concentration (t), apparent volume of distribution (VdF) and elimination half-life (t) were not significantly different. Body weight and the drug main elimination pathway contributed to sex-related differences in C and AUC. Relative to men, women had a modest increase in C with increasing age (r = 0.19, p = 0.04). Conversely, sex-related differences in AUC remained constant with increasing age.
The pharmacokinetic differences between women and men were modest and, with the exception of C, remained constant with increasing age. The higher plasma concentration might be correlated to more adverse events in older women and thus, drug treatment should be started on the lower recommended dosage when appropriate particularly for drugs characterized by a narrow therapeutic index.
女性比例随年龄增长而增加，但老年女性在临床试验中往往代表性不足。因此，人们对性别和年龄相关的生理变化对药物药代动力学的综合影响知之甚少。
我们编译了研究性别相关药代动力学差异的临床研究，这些研究同时涉及老年和年轻女性及男性。我们计算了各年龄段的各种药代动力学参数的女性/男性比值，以评估药物药代动力学随年龄变化的性别差异。我们使用方差分析探讨了体重和药物特征对性别相关药代动力学差异的贡献。
我们发现了 67 项研究报告了 56 种药物在老年和年轻女性及男性中的药代动力学数据。与男性相比，女性的峰浓度（C）（中位数（四分位距（IQR））和药物暴露量（AUC）（IQR）中位数分别高 22%（8-41%）和 20%（0-39%），而达峰时间（t）、表观分布容积（VdF）和消除半衰期（t）则无显著差异。体重和药物主要消除途径对 C 和 AUC 的性别差异有贡献。与男性相比，女性随年龄增长 C 略有增加（r = 0.19，p = 0.04）。相反，AUC 的性别差异随年龄增长保持不变。
女性与男性之间的药代动力学差异较小，除 C 外，这些差异随年龄增长保持不变。较高的血浆浓度可能与老年女性更多的不良反应有关，因此，在适当的情况下，尤其是对于治疗指数较窄的药物，应根据较低的推荐剂量开始药物治疗。
