Bioequivalence of a medicinal product PERINDOPRES A (perindopril and amlodipine fixed-dose combination) to the original medicinal product Bi-PRESTARIUM®: the results of a randomized crossover clinical trial in healthy volunteers

March 3, 2020
700
Resume

The aim was to prove the bioequivalence of the test medicinal product PERINDOPRES A, 8 mg perindopril tert-butylamine/10 mg amlodipine tablets, manufactured by PrJSC «Pharmaceutical Firm «Darnitsa» (Ukraine) and the reference medicinal product Bi-PRESTARIUM®, 10 mg perindipril arginine/10 mg amlodipine tablets, manufactured by Servier (Ireland) Industries Ltd (Ireland) in a comparative randomized two-period two-sequence (TR/RT) crossover clinical trial in healthy volunteers. Materials and methods. During each period, male and female volunteers took 1 tablet of the test or reference medicinal products in the fasting condition. Blood samples were taken within 72 hours. Quantitative determination of perindopril and amlodi­pine in blood plasma of the volunteers was performed using high-performance liquid chromatography with tandem mass spectrometric detection. Results. Data from 42 or 41 healthy volunteers were included in pharmacokinetics analysis of perindopril and amlodipine, respectively. For perindopril and amlodipine, corresponding mean Cmax values were 89.43±29.17 and 5.798±1.430 ng/mL for the test medicinal product PERINDOPRES A and 91.02±26.05 and 5.748±1.386 ng/mL for the reference medicinal product Bi-PRESTARIUM®. Mean perindopril AUC0–t and mean amlodipine AUC0–72 values were 97.67±30.95 and 219.293±65.274 ng‧h/mL, respectively, after a single dose of test medicinal product and 102.74±31.98 and 215.675±61.202 ng‧h/mL, respectively, after a single dose of reference medicinal product. Ranges of 90% confidence intervals of PERINDOPRES A/Bi-PRESTARIUM® geometric mean ratios for Cmax (91.80–103.13% for perindopril and 96.43–104.86% for amlodipine), AUC0–t for perindopril (92.09–97.85%), and AUC0–72 for amlodipine (98.28–103.99%) meet prespecified acceptance criterion for bioequivalence (80.00–125.00%). Ranges of 90% confidence intervals of test/reference geometric mean ratios for Cmax (92.66–103.07%) and AUC0–72 (94.91–99.85%) of perindoprilat (an active metabolite of perindopril) also meet the criterion and additionally support the bioequivalence. Conclusions. The bioequivalence of generic medicinal product PERINDOPRES A, 8 mg perindopril tert-butylamine/10 mg amlodipine tablets, and reference medicinal product Bi-PRESTARIUM®, 10 mg perindopril arginine/10 mg amlodi­pine tablets, was proven according to the up-to-date regulatory standards.

Published: 03.03.2020

 

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