Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males
Abstract Females present a higher risk of adverse drug reactions. Sex‐related 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 anthropomet...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-05-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13497 |
| _version_ | 1797828860815867904 |
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| author | Jessica Hindi Marc‐Olivier Pilon Maxime Meloche Grégoire Leclair Essaïd Oussaïd Isabelle St‐Jean Martin Jutras Marie‐Josée Gaulin Ian Mongrain David Busseuil Jean Lucien Rouleau Jean‐Claude Tardif Marie‐Pierre Dubé Simon deDenus |
| author_facet | Jessica Hindi Marc‐Olivier Pilon Maxime Meloche Grégoire Leclair Essaïd Oussaïd Isabelle St‐Jean Martin Jutras Marie‐Josée Gaulin Ian Mongrain David Busseuil Jean Lucien Rouleau Jean‐Claude Tardif Marie‐Pierre Dubé Simon deDenus |
| author_sort | Jessica Hindi |
| collection | DOAJ |
| description | Abstract Females present a higher risk of adverse drug reactions. Sex‐related 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‐related differences in concentrations and dosing for metoprolol and oxypurinol, the active metabolite of allopurinol. We conducted an analysis of two cross‐sectional studies. Participants were self‐described “White” 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‐ and dose‐adjusted concentrations of both metoprolol and oxypurinol (both p < 0.03). Accordingly, females presented higher unadjusted and age‐adjusted concentration:dose ratio of both metoprolol and allopurinol/oxypurinol compared to males (all p < 3.0 × 10−4). Sex remained an independent predictor of metoprolol concentrations (p < 0.01), 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‐inferred phenotype were associated with concentrations of metoprolol (all p < 0.01). Daily dose, weight, estimated glomerular filtration rate (eGFR), and employment status were associated with oxypurinol concentrations (all p < 0.01). Females present higher dose‐adjusted concentrations of metoprolol and oxypurinol than males. This suggests the need for sex‐specific dosing requirements for these drugs, although this hypothesis should be validated in prospective studies. |
| first_indexed | 2024-04-09T13:11:10Z |
| format | Article |
| id | doaj.art-58f822ad9b2840d0901676770757397e |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-04-09T13:11:10Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-58f822ad9b2840d0901676770757397e2023-05-12T07:05:38ZengWileyClinical and Translational Science1752-80541752-80622023-05-0116587288510.1111/cts.13497Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than malesJessica Hindi0Marc‐Olivier Pilon1Maxime Meloche2Grégoire Leclair3Essaïd Oussaïd4Isabelle St‐Jean5Martin Jutras6Marie‐Josée Gaulin7Ian Mongrain8David Busseuil9Jean Lucien Rouleau10Jean‐Claude Tardif11Marie‐Pierre Dubé12Simon deDenus13Faculty of Pharmacy Université de Montréal Montreal, Quebec CanadaFaculty of Pharmacy Université de Montréal Montreal, Quebec CanadaFaculty of Pharmacy Université de Montréal Montreal, Quebec CanadaFaculty of Pharmacy Université de Montréal Montreal, Quebec CanadaMontreal Heart Institute Montreal, Quebec CanadaFaculty of Pharmacy Université de Montréal Montreal, Quebec CanadaFaculty of Pharmacy Université de Montréal Montreal, Quebec CanadaMontreal Heart Institute Montreal, Quebec CanadaMontreal Heart Institute Montreal, Quebec CanadaMontreal Heart Institute Montreal, Quebec CanadaMontreal Heart Institute Montreal, Quebec CanadaMontreal Heart Institute Montreal, Quebec CanadaMontreal Heart Institute Montreal, Quebec CanadaFaculty of Pharmacy Université de Montréal Montreal, Quebec CanadaAbstract Females present a higher risk of adverse drug reactions. Sex‐related 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‐related differences in concentrations and dosing for metoprolol and oxypurinol, the active metabolite of allopurinol. We conducted an analysis of two cross‐sectional studies. Participants were self‐described “White” 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‐ and dose‐adjusted concentrations of both metoprolol and oxypurinol (both p < 0.03). Accordingly, females presented higher unadjusted and age‐adjusted concentration:dose ratio of both metoprolol and allopurinol/oxypurinol compared to males (all p < 3.0 × 10−4). Sex remained an independent predictor of metoprolol concentrations (p < 0.01), 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‐inferred phenotype were associated with concentrations of metoprolol (all p < 0.01). Daily dose, weight, estimated glomerular filtration rate (eGFR), and employment status were associated with oxypurinol concentrations (all p < 0.01). Females present higher dose‐adjusted concentrations of metoprolol and oxypurinol than males. This suggests the need for sex‐specific dosing requirements for these drugs, although this hypothesis should be validated in prospective studies.https://doi.org/10.1111/cts.13497 |
| spellingShingle | Jessica Hindi Marc‐Olivier Pilon Maxime Meloche Grégoire Leclair Essaïd Oussaïd Isabelle St‐Jean Martin Jutras Marie‐Josée Gaulin Ian Mongrain David Busseuil Jean Lucien Rouleau Jean‐Claude Tardif Marie‐Pierre Dubé Simon deDenus Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males Clinical and Translational Science |
| title | Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males |
| title_full | Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males |
| title_fullStr | Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males |
| title_full_unstemmed | Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males |
| title_short | Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males |
| title_sort | females present higher dose adjusted drug concentrations of metoprolol and allopurinol oxypurinol than males |
| url | https://doi.org/10.1111/cts.13497 |
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