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Sex Differences in Pharmacokinetics and Pharmacodynamics

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Abstract

Significant differences that exist between the sexes affect the prevalence, incidence and severity of a broad range of diseases and conditions. Men and women also differ in their response to drug treatment. It is therefore essential to understand these reactions in order to appropriately conduct risk assessment and to design safe and effective treatments. Even from that modest perspective, how and when we use drugs can result in unwanted and unexpected outcomes. This review summarizes the sex-based differences that impact on pharmacokinetics, and includes a general comparison of clinical pharmacology as it applies to men, women and pregnant women. Sex-related or pregnancy-induced changes in drug absorption, distribution, metabolism and elimination, when significant, may guide changes in dosage regimen or therapeutic monitoring to increase its effectiveness or reduce potential toxicity. Given those parameters, and our knowledge of sex differences, we can derive essentially all factors necessary for therapeutic optimization.

Since this is a rapidly evolving area, it is essential for the practitioner to review drug prescribing information and recent literature in order to fully understand the impact of these differences on clinical therapeutics.

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Acknowledgements

The authors have no conflicts of interest that are directly relevant to the content of this review. Dr Soldin is partially supported by a Clinical Investigator Award from the Flight Attendant Medical Research Institute (FAMRI; Miami, FL, USA) and grant no. 5U10HD047890-S from the National Institutes of Health/National Institute of Child Health and Human Development Obstetrics-Fetal Pharmacology Research Unit (OPRU) Network (Rockville, MD, USA) and the Office of Research on Women’s Health (Bethesda, MD, USA).

The authors wish to thank Drs Anne Zajicek and Alexander Vinks for reading the manuscript critically, and Mr Daniel O’Mara for helping with manuscript preparation.

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Correspondence to Offie P. Soldin.

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Soldin, O.P., Mattison, D.R. Sex Differences in Pharmacokinetics and Pharmacodynamics. Clin Pharmacokinet 48, 143–157 (2009). https://doi.org/10.2165/00003088-200948030-00001

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