Key Points
- To evaluate the impact of gender on labetalol pharmacokinetics and the kinetics of its individual stereoisomers in hypertensive patients.
- Conducted an evaluation within a randomized, crossover study of 19 hypertensive patients (14 men, 5 women; 6 Black, 13 White) at an academic medical center.
- Titrated labetalol to an antihypertensive target, followed by 24-hour ambulatory blood pressure monitoring and pharmacokinetic sampling.
- Quantified total labetalol concentrations and stereoisomer ratios in plasma using achiral and chiral high-performance liquid chromatography with fluorescence detection.
- Total dose-corrected labetalol AUC was 80% higher in women than in men (AUC/dose × 1000: 6.79 ± 2.11 vs 3.82 ± 1.37 hr/L, p < 0.05), despite equivalent 24-hour ambulatory blood pressure responses.
- Concentrations of the active beta-blocking stereoisomer R,R-labetalol did not differ significantly between women and men (AUC/dose × 1000: 3.91 ± 2.57 vs 3.55 ± 3.08 hr/L, p = NS).
- Concentrations were significantly elevated in women for S,R-labetalol (7.55 ± 1.47 vs 4.83 ± 1.54 hr/L, p < 0.05) and S,S-labetalol (8.23 ± 2.93 vs 4.65 ± 1.78 hr/L, p < 0.05), whereas R,S-labetalol differences were nonsignificant (6.99 ± 3.30 vs 4.25 ± 2.35 hr/L, p = 0.11).
Structured PICO
Does gender impact labetalol kinetics and stereoisomer ratios in hypertensive patients?
PPopulation19 hypertensive patients (14 men, 5 women; 6 blacks, 13 whites)
IInterventionLabetalol dosages titrated to a specific antihypertensive response
OOutcomeLabetalol plasma concentrations and stereoisomer ratiossurrogate
Gender differences in total labetalol concentrations are driven by inactive and alpha1-blocking stereoisomers, highlighting the importance of stereoisomer kinetics for racemic drugs.