ISSN: 2578-4803
Authors: Yoosakul E, Vattanarongkup J, Kunsa-ngiem S, Suthepakul N, Karachot B, Khaowroongrueng V*, Techatanawat I, Puranajoti P and Surawattanawan P
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: AUC0−tlast, AUC0− and Cmax 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 AUC0−tlast, 92.28- 98.43% for AUC0−, and 81.82-94.26% for Cmax. 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.
Keywords: Oseltamivir; Bioequivalence; Pharmacokinetics; LC-MS/MS
