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Harnessing Clinical Trial and Real-World Data Towards an Understanding of Sex Effects on Drug Pharmacokinetics, Pharmacodynamics and Efficacy
Increasing clinical data on sex-related differences in drug efficacy and toxicity has highlighted the importance of understanding the impact of sex on drug pharmacokinetics and pharmacodynamics. Intrinsic differences between males and females, such as different CYP enzyme activity, drug transporter...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207260/ https://www.ncbi.nlm.nih.gov/pubmed/35734405 http://dx.doi.org/10.3389/fphar.2022.874606 |
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author | Oi Yan Chan, Joyce Moullet, Marie Williamson, Beth Arends, Rosalinda H. Pilla Reddy, Venkatesh |
author_facet | Oi Yan Chan, Joyce Moullet, Marie Williamson, Beth Arends, Rosalinda H. Pilla Reddy, Venkatesh |
author_sort | Oi Yan Chan, Joyce |
collection | PubMed |
description | Increasing clinical data on sex-related differences in drug efficacy and toxicity has highlighted the importance of understanding the impact of sex on drug pharmacokinetics and pharmacodynamics. Intrinsic differences between males and females, such as different CYP enzyme activity, drug transporter expression or levels of sex hormones can all contribute to different responses to medications. However, most studies do not include sex-specific investigations, leading to lack of sex-disaggregated pharmacokinetic and pharmacodynamic data. Based available literature, the potential influence of sex on exposure-response relationship has not been fully explored for many drugs used in clinical practice, though population-based pharmacokinetic/pharmacodynamic modelling is well-placed to explore this effect. The aim of this review is to highlight existing knowledge gaps regarding the effect of sex on clinical outcomes, thereby proposing future research direction for the drugs with significant sex differences. Based on evaluated drugs encompassing all therapeutic areas, 25 drugs demonstrated a clinically meaningful sex differences in drug exposure (characterised by ≥ 50% change in drug exposure) and this altered PK was correlated with differential response. |
format | Online Article Text |
id | pubmed-9207260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92072602022-06-21 Harnessing Clinical Trial and Real-World Data Towards an Understanding of Sex Effects on Drug Pharmacokinetics, Pharmacodynamics and Efficacy Oi Yan Chan, Joyce Moullet, Marie Williamson, Beth Arends, Rosalinda H. Pilla Reddy, Venkatesh Front Pharmacol Pharmacology Increasing clinical data on sex-related differences in drug efficacy and toxicity has highlighted the importance of understanding the impact of sex on drug pharmacokinetics and pharmacodynamics. Intrinsic differences between males and females, such as different CYP enzyme activity, drug transporter expression or levels of sex hormones can all contribute to different responses to medications. However, most studies do not include sex-specific investigations, leading to lack of sex-disaggregated pharmacokinetic and pharmacodynamic data. Based available literature, the potential influence of sex on exposure-response relationship has not been fully explored for many drugs used in clinical practice, though population-based pharmacokinetic/pharmacodynamic modelling is well-placed to explore this effect. The aim of this review is to highlight existing knowledge gaps regarding the effect of sex on clinical outcomes, thereby proposing future research direction for the drugs with significant sex differences. Based on evaluated drugs encompassing all therapeutic areas, 25 drugs demonstrated a clinically meaningful sex differences in drug exposure (characterised by ≥ 50% change in drug exposure) and this altered PK was correlated with differential response. Frontiers Media S.A. 2022-06-06 /pmc/articles/PMC9207260/ /pubmed/35734405 http://dx.doi.org/10.3389/fphar.2022.874606 Text en Copyright © 2022 Oi Yan Chan, Moullet, Williamson, Arends and Pilla Reddy. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Oi Yan Chan, Joyce Moullet, Marie Williamson, Beth Arends, Rosalinda H. Pilla Reddy, Venkatesh Harnessing Clinical Trial and Real-World Data Towards an Understanding of Sex Effects on Drug Pharmacokinetics, Pharmacodynamics and Efficacy |
title | Harnessing Clinical Trial and Real-World Data Towards an Understanding of Sex Effects on Drug Pharmacokinetics, Pharmacodynamics and Efficacy |
title_full | Harnessing Clinical Trial and Real-World Data Towards an Understanding of Sex Effects on Drug Pharmacokinetics, Pharmacodynamics and Efficacy |
title_fullStr | Harnessing Clinical Trial and Real-World Data Towards an Understanding of Sex Effects on Drug Pharmacokinetics, Pharmacodynamics and Efficacy |
title_full_unstemmed | Harnessing Clinical Trial and Real-World Data Towards an Understanding of Sex Effects on Drug Pharmacokinetics, Pharmacodynamics and Efficacy |
title_short | Harnessing Clinical Trial and Real-World Data Towards an Understanding of Sex Effects on Drug Pharmacokinetics, Pharmacodynamics and Efficacy |
title_sort | harnessing clinical trial and real-world data towards an understanding of sex effects on drug pharmacokinetics, pharmacodynamics and efficacy |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207260/ https://www.ncbi.nlm.nih.gov/pubmed/35734405 http://dx.doi.org/10.3389/fphar.2022.874606 |
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