Bioequivalence study of a new fixed-dose combination tablet containing irbesartan and hydrochlorothiazide in healthy volunteers

Abstract Background and objective: The combination antihypertensive therapy has shown greater blood pressure lowering potential as well as better adherence to the treatment. Therefore, a new generic fixed-dose combination containing irbesartan and hydrochlorothiazide was developed and rate and extend of absorption were compared with reference formulation to prove its bioequivalence in healthy volunteers. Methods A single-center, open-label, randomized, two-period, crossover, single dose study under fasting conditions, including at least 7-days washout period, was performed in 30 healthy male and female volunteers. Twenty blood samples were collected in each study period: prior to dosing (0:00) and up to 72:00 hours after dosing and plasma concentrations of irbesartan and hydrochlorothiazide were analyzed using preliminary validated methods. Results The 90% CIs for the geometric mean ratios of test and reference of Cmax and AUC0 − t were 89.22–98.80% and 100.58–115.11%, respectively, for irbesartan and 91.80–122.96% and 94.88–117.56%, respectively. Thus, the corresponding ratios of Cmax and AUC0 − t for irbesartan and hydrochlorothiazide 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 the test and reference products demonstrated good tolerability profile in this population, and no serious AEs were observed. Conclusions Therefore, the test product (Irbesartan/hydrochlorothiazide 300/25 mg film-coated tablets, manufactured by Tchaikapharma High Quality Medicines Inc., Bulgaria) and the reference product (CoAprovel 300/25 mg film-coated tablets, manufactured by Sanofi Clir SNC, France) are considered bioequivalent.