Bioequivalence and pharmacokinetics of two formulations of amlodipine tablets in healthy subjects

Abstract EN

The bioequivalence of a single dose tablet containing 5 mg amlodipine as a test product in comparison to Norvasc® 5 mg tablet (Pfizer USA) as the reference product was studied.

Both products were administered to twenty eight healthy male adult subjects applying a fasting, single-dose, two-treatment, two-period, two-sequence, randomized crossover design with two weeks washout period between dosing.

Twenty blood samples were withdrawn from each subject over 144 hours period.

Amlodipine concentrations were determined in plasma by a validated HPLC-MS/MS method.

From the plasma concentration-time data of each individual, the pharmacokinetic parameters ; Cmax, Tmax, AUC0-t, AUC0-, Cmax / AUC0-, Z, T0.5, MRT, Cl / F and Vd / F ; were calculated applying non-compartmental analysis.

The average values of the above parameters for the test formula were 1.99 ng / ml, 8.3 hours, 82.87 ng.hr / ml, 95.23 ng.hr / ml, 0.0219 hr-1, 0.018 hr-1, 38.5 hr, 56.2 hr, 60.9 l / hr and 3483 liters, respectively.

The average values of these parameter for the reference formula were 1.92 ng / ml, 7.9 hours, 76.3 ng.hr / ml, 89.31 ng.hr / ml, 0.0225hr-1, 0.019 hr-1, 36.7 hr, 59.9 hr, 69.5 l / hr, and 3983.4 liters, respectively.

The pharmacokinetic parameters mentioned above were statistically analyzed by ANOVA test.

Ln-transformed values of the pharmacokinetic parameters used for bioequivalence testing; Cmax, AUC0-t and AUC0- ; were also statistically analyzed by ANOVA, 90 % Confidence Interval (CI) and Schuirmann’s two one-sided t-tests.

For the Tmax, parametric and nonparametric tests were applied.

Based on FDA criteria on bioequivalence, the results of the above statistical tests demonstrated bioequivalence of the two products.