Bioequivalence Study of 10 mg Ramipril Tablets in Healthy Thai Volunteers

Abstract

Objective: To determine the bioequivalence of 10 mg dose of ramipril tablets between the test product (Ramtace® 10 mg, Unison Laboratories, Thailand) and the reference product (Tritace® 10 mg, Aventis Pharma SPA, Italy). Material and Method: The present study was carried out with a single dose, 2-treatment, 2-period, 2-sequence randomized crossover design under fasting condition with a minimum of 14 days washout period in 24 healthy Thai male and female volunteers. Plasma samples for determination of ramipril and ramiprilat were obtained pre-dose and at frequent intervals for up to 72 h post dose. Ramipril and ramiprilat plasma concentrations were quantified by a validated method employing high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). All of the pharmacokinetic parameters were investigated using non-compartmental analysis. Results: The result demonstrated the 90% confidence interval (90%CI) of the geometric mean ratio (test/reference) of C max , AUC 0-72 and AUC 0-∞ of ramipril were 97.26% (84.50%-111.93%), 100.70% (89.47%-113.34%) and 100.29% (88.90%-113.15%), respectively. For ramiprilat, the 90% CI for C max , AUC 0-72 and AUC 0-∞ were 108.87% (103.00%-115.07%), 104.93% (100.50%-109.55%) and 103.30% (98.03%-108.85%), respectively. Conclusion: the 90% confidence intervals for log-transformed geometric mean test/reference formulation ratios of primary parameters were entirely within 80.00%-125.00%. Thus, it can be concluded that the test formulation was bioequivalent to the reference formulation.