AIMS: 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.
RCT Entities:
AIMS: 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.