Pharmacokinetic and Pharmacodynamic Comparative Study of Amlodipine Adipate and Amlodipine Besylate

아디핀산 암로디핀 및 베실산 암로디핀의 약동학/약력학적 특성에 관한 비교 연구

Background: Amlodipine is a dihydropyridine calcium antagonist used for the treatment of hypertension and angina. Amlodipine adipate is a newly developed salt formulation of amlodipine. The purpose of this study was to compare the pharmacokinetic and pharmacodynamic characteristics of amlodipine adipate with those of conventional amlodipine besylate in healthy subjects. Methods: The study was conducted as a single blinded, block dose randomized, two-way crossover design. Twenty-four subjects were enrolled, twelve subjects each for the 5 mg dose group and the 10 mg dose group. Subjects were administered single oral dose of amlodipine adipate and amlodipine besylate, in a randomized sequence, with two weeks washout period between the two treatments. Serial blood samples were collected till 120 hours after drug administration. Plasma concentrations of amlodipine were analyzed by liquid chromatography tandem mass spectrometry. Individual pharmacokinetic parameters were calculated by noncompartmental methods and the pharmacokinetic parameters were analyzed by analysis of variance. Ambulatory blood pressure and computerized impedance cardiography were measured till 24 hours after drug administration. The pharmacodynamic parameters were analyzed by repeated-measures analysis of variance. Results: In the 5 mg dose group, the ratios of $AUC_{last}$ and $C_{max}$ of amlodipine adipate to amlodipine besylate were 0.93 and 0.89, respectively. In the 10 mg dose group, the ratios of $AUC_{last}$ and $C_{max}$ of amlodipine adipate to amlodipine besylate were 1.01 and 1.09, respectively. Regarding pharmacodynamic results, there were no significant differences in systolic blood pressure, diastolic blood pressure, pulse rate, or in change of total peripheral resistance between amlodipine adipate and amlodipine besylate at doses of both 5 mg and 10 mg. Conclusions: We concluded that amlodipine adipate and amlodipine besylate showed similar pharmacokinetic and pharmacodynamic characteristics.