Comparative Bioavailability of Two Amlodipine Formulations in Healthy Volunteers

Abstract

The present study was conducted to find out whether the bioavailability of a 10 mg amlodipine (CAS 88150-42-9) tablet (In-tervask^©, “test”) was equivalent to that that of a reference formulation (“reference”). The pharmacokinetic parameters assessed in this study were area under the serum concentration-time curve from time zero to 144 h (AUC_t), area under the serum concentration-time curve from time zero to infinity (AUC_lnf), the peak serum concentration of the drug (C_max), time needed to achieve the peak serum concentration (t_max), and elimination half life (t_1/2).

This was a cross-over, randomized, single-blind study which included 12 healthy male and female volunteers under fasting condition. In each of the two study periods (separated by a washout of 3 weeks) a single dose of test or reference drug was administered. Blood samples were taken up to 144 h post dose, the plasma was separated and the concentrations of amlodipine were determined by a LC/MS method.

The mean AUC_t, AUC_lnf, C_max, and t_1/2 were 353.15 ng · h/mL, 417.86 ng · h/mL, 8.08 ng/mL, and 48.04 h, respectively, for the test drug and 359.99 ng · h · ml”¹, 408.23 ng · h/mL, 8.22 ng/mL, and 43.81 h, respectively, for the reference drug.

The median T_max of the test drug and reference drug were 8.0 h and 8.5 h, respectively. The point estimators of the ratios test/reference drug for AUC_t, AUC_lnf, and C_max were 96,26% , 99.48%, and 97.03 %, respectively. Furthermore, the 90% confidence intervals of the mean ratio of In-transformed were 83.73-110.68% for AUC_t, 81.79-120.99% for AUC_lnf, and 81.94–114.81 % for C_max.

It can be concluded that the two amlodipine tablets (test drug and reference drug) are bioequivalent in terms of the rate and extent of absorption.

Key words

Amlodipine, besylate salt, bioavailability, bioequivalence, pharmacokinetics - Calcium antagonists, dihydropyridine - CAS 88150-42-9 - CAS 111470-99-6 - Intervask©