Bioequivalence of Oseltamivir Phosphate 6 mg/mL Powder for Oral Suspension Formulations in Healthy Thai Volunteers under Fasting Conditions

Abstract

Oseltamivir is an oral antiviral of choice indicated for treatment and prophylaxis of influenza A and B infections. Oseltamivir is an inactive prodrug of oseltamivir carboxylate, an active form exerting antiviral activity. Oseltamivir oral suspension is an alternative formulation for pediatric patients or adults with dysphagia. GPO-A-FLU ® , oseltamivir 6 mg/mL powder for oral suspension had been developed as a generic substitute for reference product, Tamiflu ® oral suspension. In this study, we investigated the pharmacokinetics and bioequivalence of the test oral suspension oseltamivir formulation with respect to the corresponding reference oral suspension formulation. A comparative open-label, randomized, single dose, two-way crossover study was conducted under fasting conditions. Blood samples were collected for 24 hours post-dose and the plasma was separated for oseltamivir assay using a validated liquid chromatography-mass spectrometry method. The pharmacokinetic parameters were determined from plasma concentration-time profiles after administration of the test and reference formulations. The pharmacokinetic parameters were in agreement with the previously published data. The primary pharmacokinetic parameters: AUC 0−tlast , AUC 0−  and C max obtained from 47 subjects who completed the study were statistically compared. The 90% confidence intervals of geometric least squares mean ratio (test/reference) for log-transformed parameters were within 80.00-125.00% of bioequivalence criteria: 92.33-98.52% for AUC 0−tlast , 92.28- 98.43% for AUC 0−  , and 81.82-94.26% for C max . Both products were generally well tolerated by healthy Thai subjects. This study successfully demonstrated bioequivalence between GPO-A-FLU ® and Tamiflu ® , and supported product registration.