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Sex Differences in Pharmacokinetics.

Irving Zucker1, Brian J Prendergast2

  • 1Departments of Psychology and Integrative Biology, University of California, Berkeley, CA, USA. irvzuck@berkeley.edu.

Handbook of Experimental Pharmacology
|July 13, 2023
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Summary
This summary is machine-generated.

Women often experience higher drug concentrations and longer elimination times than men, leading to more adverse drug reactions. Standard dosing neglects these pharmacokinetic sex differences, risking overmedication and harm in women.

Keywords:
Adverse drug reactionsDrugsPharmacokineticsSex differences

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Area of Science:

  • Pharmacology
  • Clinical Pharmacology
  • Drug Safety

Background:

  • Limited inclusion of women in clinical trials restricts understanding of sex-based pharmacokinetic differences.
  • Existing data reveal significant pharmacokinetic (PK) sex disparities for numerous drugs.

Purpose of the Study:

  • To analyze the extent and clinical implications of pharmacokinetic sex differences in drug disposition.
  • To evaluate the relationship between PK sex differences and sex-specific adverse drug reactions (ADRs).

Main Methods:

  • Analysis of a 2020 dataset examining PK sex differences for 86 drugs.
  • Correlation of PK variations with reported incidence of ADRs stratified by sex.

Main Results:

  • Women typically exhibit higher blood concentrations and prolonged drug elimination compared to men for many medications.
  • A strong association exists between higher PK values in women and increased ADR incidence in females (96%).
  • Conversely, male-biased ADRs were poorly predicted when men had higher PK values (29%).

Conclusions:

  • Sex differences in pharmacokinetics are prevalent and clinically significant, contributing to sex-specific ADR patterns.
  • Current uniform dosing practices overlook PK variations, potentially leading to female overmedication and increased ADRs.
  • Evidence-based, sex-specific dosing adjustments are crucial to mitigate these risks and improve drug safety.