Pharmacokinetics and bioequivalence study of irbesartan tablets after a single oral dose of 300 mg in healthy Thai volunteers

Objective: Pharmacokinetics and bioequivalence of 300 mg irbesartan tablets were studied in 26 healthy Thai male volunteers. Methods: A single oral dose of one 300 mg tablet of the test product and the reference product was given to each volunteer according to a randomized two-way crossover design with 1-week wash out period. Blood samples were collected at predetermined time intervals until 72 hours post dose and irbesartan concentration was quantified with a validated HPLC method. Individual plasma irbesartan concentration-time profile was analyzed for pharmacokinetic parameters. Results: Maximum plasma concentrations (C-max) of 3,617.19 and 3,295.77 ng/mL for test and reference, respectively, were achieved. Areas under the plasma concentration-time curve; AUC(0-t), and AUC(0-infinity) were 15,304.65 and 15,638.90 ngxh/mL for test and 15,389.21 and 15,730.34 ngxh/mL for reference. The median t(max) was 1.50 hours and 1.25 hours for test and reference, respectively. Plasma elimination half-lives (t(1/2)) were 7.35 hours and 8.09 hours for test and reference, respectively. Primary pharmacokinetic parameters C-max, AUC(0-t), and AUC(0-infinity), were tested parametrically by analysis of variance (ANOVA), and it revealed no statistically significant difference (defined as p <0.05) between the corresponding C-max, AUC(0-t), and AUC(0-infinity), with respect to sequence, volunteers, period and formulation. The 90% confidence intervals for the ratio of test and reference product of the parameters C-max, AUC(0-t), and AUC(0-infinity) were within 80 - 125% (100.13 - 121.40% for C-max, 90.83 - 106.86% for AUC(0-t) and 91.11 - 106.55% for AUC(0-infinity)). Conclusion: The two products were bioequivalent in terms of both rate and extent of drug absorption into systemic circulation.