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Sex-related pharmacokinetic differences with aging

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Key summary points

AbstractSection Aim

To evaluate the combined effect of sex- and age-related physiological and biological changes on drug pharmacokinetics.

AbstractSection Findings

Median peak concentration and drug exposure were on average 22% and 20% higher in women compared with men. With increasing age, sex differences in peak concentration tended to be more pronounced but remained similar for drug exposure.

AbstractSection Message

The pharmacokinetic differences between women and men are modest and, with the exception of peak concentration, remain constant with increasing age.

Abstract

Purpose

The proportion of women increases with advanced age, but older women are often underrepresented in clinical trials. Therefore, little is known about the combined effect of sex- and age-related physiological changes on drug pharmacokinetics.

Methods

We compiled clinical studies, which investigated sex-related pharmacokinetic differences both in older and young women and men. The ratio women/men was calculated for various pharmacokinetic parameters across adulthood to assess sex-related differences in drug pharmacokinetics with aging. The contribution of body weight and drug characteristics to sex-related pharmacokinetic differences were explored using analysis of variance.

Results

We found 67 studies reporting the pharmacokinetics for 56 drugs both in older and young women and men. Median peak concentration (Cmax) (interquartile range (IQR)) and drug exposure (AUC) (IQR) were 22% (8–41%) and 20% (0–39%) higher in women compared with men whereas time to peak concentration (tmax), apparent volume of distribution (VdF) and elimination half-life (t1/2) were not significantly different. Body weight and the drug main elimination pathway contributed to sex-related differences in Cmax and AUC. Relative to men, women had a modest increase in Cmax with increasing age (r = 0.19, p = 0.04). Conversely, sex-related differences in AUC remained constant with increasing age.

Conclusion

The pharmacokinetic differences between women and men were modest and, with the exception of Cmax, remained constant with increasing age. The higher plasma concentration might be correlated to more adverse events in older women and thus, drug treatment should be started on the lower recommended dosage when appropriate particularly for drugs characterized by a narrow therapeutic index.

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Availability of data and material

The data that support the findings of this study are available in the article and supplementary material of this article.

Code availability

The mathematical code for the statistical analysis is available from the corresponding author upon reasonable request.

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Funding

The study was financially supported by the Swiss National Science Foundation (Grant no. 166204), the OPO Foundation, and the Isaac Dreyfus Foundation.

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Author notes

  1. Felix Stader

    Present address: Simcyp Division, Certara UK Ltd., Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, England

Authors and Affiliations

  1. Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland

    Felix Stader & Catia Marzolini

  2. University of Basel, Basel, Switzerland

    Felix Stader & Catia Marzolini

Authors
  1. Felix Stader
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  2. Catia Marzolini
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Contributions

Designed research: FS and CM; acquisition of data: FS and CM; performed research: FS; analysis and interpretation of data: FS and CM; drafting of the manuscript: FS and CM.

Corresponding author

Correspondence to Catia Marzolini.

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Supplementary file1 (DOCX 70 kb)

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Stader, F., Marzolini, C. Sex-related pharmacokinetic differences with aging. Eur Geriatr Med 13, 559–565 (2022). https://doi.org/10.1007/s41999-021-00587-0

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  • DOI: https://doi.org/10.1007/s41999-021-00587-0

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