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Sex-related pharmacokinetic differences with aging.
Felix Stader1,2,3, Catia Marzolini4,5
1Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland.
European Geriatric Medicine
|November 19, 2021
Summary
Older women show modest pharmacokinetic differences compared to men, with higher peak concentrations (Cmax) but similar elimination. Drug dosage adjustments may be needed for older women, especially for narrow therapeutic index drugs.
Area of Science:
- Pharmacology
- Gerontology
- Clinical Trials
Background:
- Older women are underrepresented in clinical trials, limiting knowledge of age- and sex-related physiological changes on drug pharmacokinetics.
- Understanding pharmacokinetic differences is crucial for safe and effective drug therapy in aging populations.
Purpose of the Study:
- To assess sex-related differences in drug pharmacokinetics across adulthood, considering aging.
- To explore the influence of body weight and drug characteristics on these differences.
Main Methods:
- Compiled 67 clinical studies on pharmacokinetics for 56 drugs in young and older women and men.
- Calculated women/men ratios for pharmacokinetic parameters (Cmax, AUC, tmax, VdF, t1/2).
- Used analysis of variance to explore contributions of body weight and drug properties.
Main Results:
- Women had higher median peak concentrations (Cmax) and drug exposure (AUC) compared to men (22% and 20% higher, respectively).
- Time to peak concentration (tmax), volume of distribution (VdF), and half-life (t1/2) did not differ significantly between sexes.
- Body weight and main drug elimination pathway influenced Cmax and AUC differences; Cmax increased modestly with age in women relative to men.
Conclusions:
- Pharmacokinetic differences between women and men are modest and largely age-independent, except for Cmax.
- Higher plasma concentrations in women may increase adverse event risk, suggesting cautious dosing, especially with narrow therapeutic index drugs.
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