Pharmacokinetics of a new amlodipine formulation: Bioequivalent and not affected by CYP3A5 genotype

Abstract

Background/Aims Amlodipine is among the most widely used antihypertensive drugs. This study aimed to compare pharmacokinetic properties of test formulation (T), amlodipine orotate, with those of reference one (R), amlodipine besylate, and to evaluate the impact of CYP3A5 genotype on the pharmacokinetics. Methods A randomized, single-blind, crossover study with a 2-week washout period was performed at the Clinical Trial Center, Seoul National University Hospital (Korea). A single 10 mg dose was administered orally to 24 healthy male volunteers with CYP3A5*1/*3 (n= 9), *3/*3 (n= 15) genotypes. After dosing, serial blood samples were collected for a period of 144h. Plasma concentrations were determined by LC/MS/MS and the pharmacokinetic parameters were analyzed by non-compartmental analysis. Results Pharmacokinetic comparison did not show differences between the formulations: area under the curve (AUCinf) 336 versus 329 ng*h/mL, maximum plasma concentration (Cmax) 6.89 versus 6.46 ng/mL, elimination half-life 44.0 versus 42.6h for T and R formulations, respectively. The geometric mean ratios (90% CI) of the AUCinf and Cmax were 1.06 (0.95–1.19) and 1.10 (0.99–1.24), respectively. These values were within the equivalence range of 0.80–1.25. Apparent clearances (CL/F) according to CYP3A5 genotype were not significantly different in both T (P=.18) and R (P=.79). Conclusions Two formulations of amlodipine are bioequivalent and their pharmacokinetics may not be affected by CYP3A5 genotype. Clinical Pharmacology & Therapeutics (2005) 77, P78–P78; doi: 10.1016/j.clpt.2004.12.189