Comparative bioavailability of two losartan formulations in healthy human volunteers after a single dose administration.

Objective: To compare the bioavailability of two potassic losartan immediate release tablet (50 mg) formulations (Losartan from Laboratórios Cristália Ltd., Brazil, as a test formulation and Cozaar® from Merck Sharp & Dohme Farmacêutica Ltd., Brazil, as a reference formulation) in 25 volunteers of both sexes. Material and methods: The study was conducted in an open, randomized, 2-period crossover design and a 1-week washout period. Plasma samples were obtained over a 24-hour interval. The concentrations of losartan and its active metabolite losartan acid were analyzed by combined reversed phase liquid chromatography and tandem mass spectrometry (LC-MS-MS) with negative ion electrospray ionization using a selected ion monitoring method. From the losartan and losartan acid plasma concentrations vs. time curves the following pharmacokinetic parameters were obtained: AUC_last, AUC_0-inf and C_max. Results: The geometric mean and respective 90% confidence interval (CI) of Losartan/Cozaar® losartan percent ratios were 92.9% (82.2 - 105.0%) for C_max, 99.0% (92.5 - 105.9%) for AUC_last, and 99.1% (92.7 - 105.8%) for AUC_0-inf. Furthermore, the geometric mean and respective 90% CI of Losartan/Cozaar® losartan acid percent ratios were 98.5% (91.5 - 106.0%) for C_mac, 97.9% (93.3 - 102.7%) for AUC_last, and 98.1% (93.6 - 102.9%) for AUC0-inf. Conclusion: Since the 90% CI for C_max, AUC_last and AUC_0-inf were within the 80 - 125% interval proposed by the US Food and Drug Administration, it was concluded that the potassic losartan immediate release 50 mg tablet was bioequivalent to the Cozaar® immediate release 50 mg tablet, according to both the rate and extent of absorption. While there were no significant differences in the bioequivalence assessed by either losartan or losartan acid, future bio equivalence studies on losartan may be performed by quantifying losartan alone as the parent compounds are more discriminative. [ABSTRACT FROM AUTHOR]