Comparative bioavailability of two ramipril formulations after single-dose administration in healthy volunteers.

Objective: To assess the bioequivalence of a ramipril 5 mg tablet formulation (ramipril test formulation from LaboratOrios Biosintetica Ltda (Sao Paulo, Brazil) and Triatec® from Aventis Pharma (Sueano, Brazil) standard reference formulation) in 26 healthy volunteers of both sexes. Methods: The study was conducted using an open, randomized, 2-period crossover design with a 2-week washout interval. Plasma samples were obtained over a 36-hour period. Plasma ramipril and ramiprilat concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the ramipril and ramiprilat plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained: AUC l a s t , AUC i n f and C m a x . Results: The limit of quantification was 0.2 ng × ml - 1 and 1.0 ng × ml - 1 for ramipril and ramiprilat, respectively. The geometric means and 90% confidence intervals (CI) for Ramipril/Triatec® and Ramiprilat/Triatec® percent ratios were: 104.69% (90% CI = 93.21 - 117.59%) for C m a x , 102.49% (90% CI = 92.76 - 113.24%) for AUC l a s t , 103.60% (90% CI = 93.56 -114.73%) for AUc i n f , 108.48% (90% CI = 98.86-119.03%) for C m a x , 105.88% (90% CI = 101.55 - 110.39%) for AUC l a s t , 97.30% (90% CI = 90.17 - 104.99%) for AUC i n f , respectively. Conclusion: Since the 90% CI for AUC l a s t , AUC i n f and C m a x ratios were within the 80 - 125% interval proposed by the US FDA, it was concluded that the ramipril formulation produced by LaboratOrios Biosintetica Ltda is bioequivalent to the Triatec® formulation in both rate and extent of absorption.