Assessment of sex differences in pharmacokinetics and pharmacodynamics of amlodipine in a bioequivalence study.
OBJECTIVE
This study was conducted to assess the bioequivalence between two 10-mg amlodipine tablet formulations. As secondary objectives, sex-related differences and tolerability profile were evaluated.


METHODS
Thirty-six healthy volunteers (18 males and 18 females; age 20-32 years, weight 49.5-98.0 kg) were included in a randomised crossover study. Subjects were administered a single 10-mg oral dose of each formulation separated by a 14-day washout period. Plasma amlodipine levels were determined by a high performance liquid chromatographic method with tandem mass spectrometry detection.


RESULTS
All subjects completed the study and 90% confidence intervals for relevant pharmacokinetic parameters were within the ranges defined by European and US Regulatory Authorities: the geometric mean and the 90% confidence interval test/reference ratios calculated from log-transformed values were 104.54 (101.46-107.72%) for AUC(0-infinity) and 100.32 (97.41-103.33%) for Cmax. There were no serious or severe adverse events. The tolerability profile appeared to be comparable for the two products. On average, bioavailability of amlodipine was slightly higher in females than in males, but these differences could be explained by the lower body weight of women. There were no sex-related differences in drug clearance. Bioequivalence was also demonstrated within each gender group. Amlodipine treatment produced a slight decrease of systolic blood pressure and an increased in heart rate, which were more pronounced in women. The incidence of adverse events was similar in men and women.


CONCLUSIONS
The two formulations were considered bioequivalent. Although there were no relevant gender-related differences in the pharmacokinetics of amlodipine, women reached higher amlodipine concentrations most likely because of their lower body weight, and therefore, the reported pharmacodynamic effects were higher within this gender group.
Abad-Santos
Francisco
F
Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Diego de León 62, 28006 Madrid, Spain. fabad.hlpr@salud.madrid.org
Novalbos
Jesús
J
Gálvez-Múgica
Maria-Angeles
MA
Gallego-Sandín
Sonia
S
Almeida
Susana
S
Vallée
François
F
García
Antonio G
AG
D000328:Adult; D017311:Amlodipine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D012737:Sex Factors; D013810:Therapeutic Equivalency
D002121:Calcium Channel Blockers; D017311:Amlodipine