Bioavailability of two oral-suspension formulations of a single dose of nitazoxanide 500 mg: An open-label, randomized-sequence, two-period crossover, comparison in healthy fasted Mexican adult volunteers

Abstract

Nitazoxanide is an oral broad-spectrum parasiticidal agent. In Mexico, the oral powder for suspension of nitazoxanide is indicated for the treatment of antiprotozoal and anthelmintic infections in patients of 1 year or older. The aims of this study were to compare the bioavailability and to determine the bioequivalence of a test and reference formulation of oral nitazoxanide 500 mg, administered as a suspension, and to generate data regarding the oral bioavailability of this drug on the Mexican population. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted on a total of 26 Mexican adult subjects of both genders, with a 1-week washout period. Study formulations were administered after a 10-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 7, 8, 9, 10 and 12 hours after administration. Plasma concentrations of tizoxanide (active metabolite of nitazoxanide) were determined using HPLC coupled to a mass spectrometry (MS/MS). The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%. The estimated pharmacokinetic parameters of tizoxanide for the reference (Daxon®) and test (Paramix®) formulations were: Cmax (10.40±2.99 μg/ml, 10.73 ± 3.45 μg/ml); AUC0-t (39.57 ± 15.89 μg•h /ml, 43.31 ± 19.13 μg•h /ml); and AUC0-∞ (40.93 ± 16.05 μg•h /ml, 45.00 ± 19.63 μg•h /ml), respectively. The 90% CIs for the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ were: 94.58%-110.21%, 100.43%-116.22%, and 101.00%-116.43%, respectively, the within-subject %CV values were 16.23, 15.49 and 15.05, respectively. All the power values were 100%. In this study a single dose of the test formulation met the regulatory requirements to assume bioequivalence, based on the rate and extent if absorption. © 2011 Balderas-Acata JI, et al.