{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:59:42Z","timestamp":1792101582174,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Females present a higher risk of adverse drug reactions. Sex\u2010related differences in drug concentrations may contribute to these observations but they remain understudied given the underrepresentation of females in clinical trials. The aim of this study was to investigate whether anthropometric and socioeconomic factors and comorbidities could explain sex\u2010related differences in concentrations and dosing for metoprolol and oxypurinol, the active metabolite of allopurinol. We conducted an analysis of two cross\u2010sectional studies. Participants were self\u2010described \u201cWhite\u201d adults taking metoprolol or allopurinol selected from the Montreal Heart Institute Hospital Cohort. A total of 1007 participants were included in the metoprolol subpopulation and 459 participants in the allopurinol subpopulation; 73% and 86% of the participants from the metoprolol and allopurinol subpopulations were males, respectively. Females presented higher age\u2010 and dose\u2010adjusted concentrations of both metoprolol and oxypurinol (both <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.03). Accordingly, females presented higher unadjusted and age\u2010adjusted concentration:dose ratio of both metoprolol and allopurinol\/oxypurinol compared to males (all <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a03.0\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>). Sex remained an independent predictor of metoprolol concentrations (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), but not of oxypurinol concentrations, after adjusting for other predictors. In addition to sex, age, daily dose, use of moderate to strong CYP2D6 inhibitors, weight, and CYP2D6 genotype\u2010inferred phenotype were associated with concentrations of metoprolol (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Daily dose, weight, estimated glomerular filtration rate (eGFR), and employment status were associated with oxypurinol concentrations (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Females present higher dose\u2010adjusted concentrations of metoprolol and oxypurinol than males. This suggests the need for sex\u2010specific dosing requirements for these drugs, although this hypothesis should be validated in prospective studies.<\/jats:p>","DOI":"10.1111\/cts.13497","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T04:40:07Z","timestamp":1677818407000},"page":"872-885","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Females present higher dose\u2010adjusted drug concentrations of metoprolol and allopurinol\/oxypurinol than males"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5394-0352","authenticated-orcid":false,"given":"Jessica","family":"Hindi","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montreal, Quebec Canada"},{"name":"Montreal Heart Institute  Montreal, Quebec Canada"},{"name":"Universit\u00e9 de Montr\u00e9al Beaulieu\u2010Saucier Pharmacogenomics Centre  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