Bioequivalence of Two Brands of Valsartan 80 mg Coated Breakable Tablets in 15 Healthy Algerian Volunteers: A Pilot Study

A randomized, two-way, crossover study was conducted in 15 fasting, healthy, Algerian volunteers to compare the bioavailability of two brands of Valsartan 80 mg coated breakable tablets. The present study aimed to evaluate the intra-subject variability of this active substance in the Algerian population. The test brand was compared to TAREG (Novartis) as the reference product. The study was performed at the bioequivalence center of the national control laboratory for pharmaceuticals products, in joint venture with University Hospital Center Ibn Badis, Constantine, Algeria. The drug was administered with 200 mL of water after a 10 h overnight fasting on two treatment days separated by one week washout period. After dosing, serial blood samples were collected for a period of 24 h. A reliable, simple, and robust liquid chromatography-tandem mass spectro-metric (LC-MS/MS) method has been developed and validated that employs protein precipitation (or denaturation) for the estimation of valsartan in human plasma using losartan as internal standard. The assay was found to be linear over the range of 50-5,000 ng/mL, with a lower limit of quantitation of 50 ng/mL. Various pharmacokinetic parameters including AUC0-t, AUC0-∞, Cmax, Tmax, and T1/2 were determined from plasma concentrations of both formulations and found to be in good agreement with reported values. The pharmacokinetical and statistical analysis was conducted with Kinetica 4.4.1. AUC0-t, AUC0-∞ and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence interval ([85.82%, 118.76%] for AUC0-t [86.09%, 118.83%] for AUC0-∞) of test/reference ratio for these parameters were found within bioequivalence acceptance range of 80-125%. But for the Cmax, the 90% confidence interval of test/reference ratio wasn't in this acceptance range [90.18%, 131.07%] .The results of PK analysis suggested that the reference and test formulations of valsartan 80 mg coated breakable tablets weren't bioequivalent during fasting state in these healthy algerian volunteers.