COMPARATIVE BIOAVAILABILITY OF TWO LOSARTAN FORMULATIONS IN HEALTHY HUMAN VOLUNTEERS AFTER A SINGLE DOSE ADMINISTRATION
Dhaneshwar Shep1*, Dixit Patel1, Manoj Karwa2, Sanjay Maroo1, Saurabh Arora2
1. Medical Services, Troikaa Pharmaceuticals Ltd., Ahmedabad
2. Auriga Research Ltd., New Delhi
The aim of this study was to evaluate the bioequivalence of test and reference losartan potassium 50 mg formulations in healthy volunteers. This open label, balanced, single-dose, randomized, 2-period, crossover oral bioequivalence study was conducted in 54 healthy human adult subjects under fasting condition. Subjects received losartan 50 mg of either test or reference formulation with a washout period of 7 days. After study drug administration, serial blood samples were collected over a period of 48 hours. The plasma concentrations of losartan and its active metabolite were determined by a validated method using LC/MS/MS. Pharmacokinetic parameters Cmax, Tmax, t1/2, AUC0-t, AUC 0-∞, and kel, were determined for both the formulations. The formulations were to be considered bioequivalent if the log-transformed ratios of Cmax, AUC0-t, and AUC0-∞ were within the predetermined bioequivalence range of 80% to 125%. A total of 54 subjects were enrolled. No significant differences were found based on analysis of variance. The mean values and 90% confidence intervals (CI) of test/reference ratios for these parameters of losartan as follows: Cmax 274.90 Vs 286.93 ng/mL (83.95 -113.69); AUC0-t 434.67 Vs 438.68 ng.hr/mL (93.30 -104.03); and AUC0-∞ 463.23 Vs 464.71 ng.hr/mL (94.65 -104.80) and for its active metabolite (losartan carboxylic acid) the mean values and 90% CI of test/reference ratios for these parameters as follows: Cmax 572.63 Vs 543.82 ng/mL (96.87-109.37); AUC0-t 3987.89 Vs 4051.07 ng.hr/mL (93.48-104.22); and AUC0-∞ 4215.58 Vs 4271.67 ng.hr/mL (94.84-105.26). This study shows that the test formulation is bioequivalent to the reference formulation for losartan and its main active metabolite.
Key Words: Bioequivalence, Losartan, losartan carboxylic acid, Pharmacokinetics.
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