生物学的同等性とバイオアベイラビリティのジャーナル

概要

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

Juana Isabel Balderas-Acata, Esteban Patricio Ríos-RogríguezBueno, Fabiola Pérez-Becerril, Clara Espinosa-Martínez, Victoria Burke- Fraga and Mario González-de la Parra

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, 5, 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: C max (10.40±2.99 μg/ml, 10.73 ± 3.45 μg/ml); AUC 0–t (39.57 ± 15.89 μg•h /ml, 43.31 ± 19.13 μg•h / ml); and AUC 0–∞ (40.93 ± 16.05 μg•h /ml, 45.00 ± 19.63 μg•h /ml), respectively. The 90% CIs for the geometric mean ratios of C max, AUC 0–t, and AUC 0–∞ 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 of absorption.