Hospital Pharmacology (Jan 2018)
Comparative bioavailability of a newly developed Irbesartan 300 mg containing preparation
Abstract
Introduction: Irbesartan (CAS registry: 138402-11-6) is a potent, orally active, selective antagonist of the angiotensin II receptors (type AT1) indicated for the treatment of arterial hypertension and chronic heart failure. Aim: The objective of the present study was to demonstrate the bioequivalence of an oral test preparation (Irbesartan 300 mg film-coated tablets Tchaikapharma High Quality Medicines Inc., Bulgaria) and a reference (Aprovel 300 mg film-coated tablets, Sanofi Clir SNC, France), by comparing the rate and extent of absorption of both products upon a single oral administration of the tablets under fasting conditions in healthy volunteers. Methodology: The study was carried out as a single-center, open-label, randomised, twoperiod, single dose, crossover oral bioequivalence study in 40 healthy male and female subjects under fasting conditions. During each study period blood samples for analysis of irbesartan were taken prior to dosing and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours after dosing. The separated plasma was analyzed in the bioanalytical division of Anapharm Europe with a validated method using reversed phase high performance liquid chromatography coupled to a tandem mass spectrometry detector (RP-LC/MS/MS). Results: The point estimates with 90% confidence intervals of the geometric mean ratios of test and reference (T/R) in the study were found to be 102.39% (95.55% - 109.71%) for Cmax and 98.56 % (92.72 % - 104.76 %) for AUC0-72. Thus, the corresponding ratios of Cmax and AUC0-72 met the predetermined criteria for bioequivalence (90% confidence intervals of the geometric mean ratios of test and reference within the 80.00% - 125.00%). Both products were generally very well tolerated. Conclusions: Irbesartan 300 mg film-coated tablets, Tchaikapharma High Quality Medicines Inc., Bulgaria) and Aprovel 300 mg film-coated tablets (Sanofi Clir SNC, France), are bioequivalent with regard to the rate and extent of absorption.
