Abstract: Amlodipine is a third-generation dihydropyridine calcium channel blocker that is indicated for treatment of hypertension and angina in adults. The population pharmacokinetics of amlodipine was evaluated in 60 healthy volunteers enrolled in three bioequivalence studies. These data, along with a set of covariates, were the subject of a nonlinear mixed-effect modeling analysis using the NONMEM program. A two-compartment model with first order absorption was fitted to the serum amlodipine concentration data. No significant covariates were found in the model-building. The intraindividual (residual) variability expressed as coefficient of variation was 18.7%, whereas the interindividual variability of CL, V₂,V₃ and K_a,was 27.3%, 26.6%, 49.9% and 65.7%, respectively. The relatively high (>40%) interindividual variability for V₃ and K_a parameters, observed under the controlled experimental settings of bioequivalence trials in healthy volunteers, may result from genetic variability of the processes involved in amlodipine absorption and disposition.

Key words: Amlodipine, Population Pharmacokinetics, NONMEM