Single-dose, randomized, crossover bioequivalence study of amlodipine maleate versus amlodipine besylate in healthy volunteers

Abstract

Amlodipine, marketed primarily as a besylate salt, is a calcium channel blocker used for treating essential hypertension. Amlodipine maleate is another salt that is considered, in terms of pharmacokinetics and pharmacodynamics, similar to amlodipine besylate. This open, randomized, two-period crossover trial has investigated in 24 healthy volunteers over a 144 h period the bioequivalence of amlodipine maleate tablets 10 mg versus amlodipine besylate tablets (Norvasc 10 mg). Plasma amlodipine concentrations were assessed by ultra performance liquid chromatography interfaced with a double quadrupole mass spectrometer. The area under the curve total (AUC(t)) and the area under the curve to infinity (AUC(inf)) values, peak plasma concentration (C(max)), and time to attain peak (t(max)) were not statistically different between the two drugs. AUC(t) and AUC(inf) values were higher (p < 0.05) in females than in males. The tolerability profile was comparable for the two salts of amlodipine. These findings indicate that amlodipine maleate and besylate are bioequivalent and were well tolerated, which suggests that the plasma kinetics of amlodipine depend on the properties of the molecule itself. Hence, the two salts investigated could be used interchangeably in clinical practice