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

Comparative Bioavailability of Two Oral Oseltamivir Formulations: Commercial Capsules and an Emergency Solution Prepared During the 2009 Influenza a (H1n1) Outbreak in Mexico

Lina Marcela Barranco-Gardu?o, Ariadna Cervantes-Nev?rez, Adrian Mart?nez-Talavera, Juan Carlos Neri-Salvador, Gilberto Casta?eda-Hern?ndez, Francisco Javier Flores-Murrieta and Miriam del Carmen Carrasco-Portugal

This study was designed to evaluate the bioequivalence of two formulations, commercially available capsule of oseltamivir phosphate and an emergency solution prepared to be used under the influenza A (H1N1) outbreak in Mexico. The clinical investigation was designed as a randomized, open-labeled, two-part, two-treatment, two- period crossover study, in 22 healthy male volunteers. Each formulation was administered with 200 ml of water after 10-hour overnight fast. After dosing, serial blood samples were collected for a period of 24 hours. Plasma concentrations were determined by a validated high-performance liquid chromatographic method with fluorescence detection and pharmacokinetic parameters were obtained by non-compartmental approach. Analysis of variance (ANOVA) was carried out using log-transformed AUC last , AUC ∞ and C max and untransformed t max , and 90% confidence intervals for AUC last , AUC ∞ and C max were calculated. If the 90% confidence intervals (CI) for AUC last , AUC ∞ and C max fell fully within the interval 80 – 125%, the bioequivalence of the two formulations was established. The means (test and reference) for AUC last were 3745.386 and 3535.320 ng.h/ml, for AUC ∞ were 3967.991 and 3911.227 ng.h/ml and for C max were 340.335 and 352.737 ng/ml. The geometric mean ratios of the test formulation to reference formulation for AUC last , AUC ∞ and C max (CI) were 101.92% (85.62 – 121.33%), 103.43% (87.29 – 122.56%) and 105.45% (90.86 – 122.39%), respectively. All 90% CI for AUC last , AUC ∞ and C max fell within the Mexican Federal Commission for Prevention of Sanitary Risks (COFEPRIS) accepted bioequivalence range of 80 – 125%. Based on the results, the formulations tested are bioequivalent.