Pilon Marc-Olivier, Hindi Jessica, St-Jean Isabelle, Jutras Martin, Brouillette Maxime Meloche, Mongrain Ian, Lagacé Caroline, Vazquez Karla, Provost Sylvie, Lemieux Perreault Louis-Philippe, Oussaid Essaid, Busseuil David, Cyr Marie-Christyne, Tardif Jean-Claude, Dubé Marie-Pierre, Leclair Grégoire, de Denus Simon
Faculty of Pharmacy, Université de Montréal, 2940 Chemin de Polytechnique, Montreal, Quebec, H3T 1J4, Canada.
Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, H1T 1C8, Canada.
Eur J Clin Pharmacol. 2025 Feb;81(2):321-332. doi: 10.1007/s00228-024-03786-3. Epub 2024 Dec 20.
Women are underrepresented in drug development trials and there is no sex-tailored drug regimen for most medications. It has been repeatedly shown that women have more adverse drug reactions than men for several medications. These differences could be explained by higher dose-adjusted drug concentrations in women. Thus, we aim to identify sex-related differences and to characterize the clinical and genetic predictors of these differences in drug concentrations, dosing, and adherence for 47 commonly used drugs in a large cohort. The objective of this article is to present an overview of the methods and characteristics of the study population.
We performed a cross-sectional study that included 10,082 men and women of European ancestry aged ≥ 18 years from the Montreal Heart Institute Hospital Cohort taking at least one of the 47 medications regularly.
Of the 10,082 participants included, 36% were women. Women had lower weight, height, waist girth, and body mass index than men, but they had higher hip girth (all p < 0.001). Men had a higher level of education and annual income and were more likely to be employed full-time compared to women. Furthermore, men had a higher prevalence of hypertension, type 2 diabetes, dyslipidemia, and myocardial infarction (all p < 0.001) and were more likely receiving lipid-lowering agents, beta-blockers, antidiabetic drugs, and angiotensin-converting enzyme inhibitors. Conversely, proton pump inhibitors were more prevalent in women. Interestingly, nearly half of the women had a history of drug allergy or intolerance, compared with less than one-third of the men (p < 0.001).
This study has a high potential in understanding eventual sex differences in drug dosing requirements and will most likely provide useful information to personalize drug regimens in women.
在药物研发试验中，女性的参与度不足，而且大多数药物都没有针对性别的用药方案。多项研究反复表明，在使用几种药物时，女性比男性更容易出现药物不良反应。这些差异可能是由于女性经剂量调整后的药物浓度较高所致。因此，我们旨在确定性别相关差异，并在一个大型队列中，对47种常用药物在药物浓度、剂量和依从性方面的这些差异的临床和遗传预测因素进行特征描述。本文的目的是概述研究人群的方法和特征。
我们进行了一项横断面研究，纳入了蒙特利尔心脏研究所医院队列中10082名年龄≥18岁、有欧洲血统的男性和女性，他们定期服用47种药物中的至少一种。
在纳入的10082名参与者中，36%为女性。女性的体重、身高、腰围和体重指数均低于男性，但臀围高于男性（所有p<0.001）。与女性相比，男性的教育水平和年收入更高，全职工作的可能性更大。此外，男性患高血压、2型糖尿病、血脂异常和心肌梗死的患病率更高（所有p<0.001），并且更有可能接受降脂药物、β受体阻滞剂、抗糖尿病药物和血管紧张素转换酶抑制剂治疗。相反，质子泵抑制剂在女性中更为普遍。有趣的是，近一半的女性有药物过敏或不耐受史，而男性这一比例不到三分之一（p<0.001）。
本研究在了解药物剂量需求中可能存在的性别差异方面具有很大潜力，很可能为女性个性化用药方案提供有用信息。
