Study of Comparative Pharmacokinetics and Bioequivalence of Drugs Amlodipine + Valsartan and Exforge®

Abstract

Objective: Drug Amlodipine+Valsartan is safe and effective for comprehensive treatment of arterial hypertension patients taken combined therapy by prescription. The development of new fix drug combination amlodipine and valsartan will provide in the near future a significant reduction in the cost of treatment. The aim of this work was investigation of bioequivalence for a generic drug Amlodipine+Valsartan, film-coated tablets, 10 mg+160 mg (Polpharma SA, Poland) and Exforge®, film-coated tablets, 10 mg+160 mg (Novartis Pharma AG, Switzerland). Materials and methods: 58 healthy volunteers were enrolled in open label, randomized, two sequence, two treatment cross-over study. Drugs were administered in two periods with a 21-day washout period in-between. Blood samples were collected over a 72-hour period. Amlodipine and Valsartan were measured in plasma using an automated LC-MS/MS assay. Pharmacokinetic parameters were calculated by non-compartmental analyses approach to evaluate AUC0-t, AUC0-∞ and Cmax. ANOVA was performed on the ln-transformed data and the 90% Confidence Interval (CI) was determined. Bioequivalence will be concluded if the 90% CI falls within 80-125% for AUC0-t and Cmax. Results: 53 volunteers completed the study and were considered for the pharmacokinetic and statistical analyses. Descriptive safety data analyses were performed on all 58 subjects. 90%-CI for corrected GMEAN of test and reference ratio was 94.76-105.24% for AUC0-t and 92.78-108.79% for Cmax in the case of amlodipine; 94.93-119.61% for AUC0-t and 90.41-116.03% for Cmax in the case of valsartan. So all pharmacokinetic parameters met the acceptance criteria as the 90% CI were within 80.00-125.00%. Conclusion: This study showed that Amlodipine+Valsartan, film-coated tablets, 10 mg+160 mg (Polpharma SA, Poland) is bioequivalent to reference product Exforge®, film-coated tablets, 10 mg+160 mg (Novartis Pharma AG, Switzerland).