Pharmacokinetics and bioequivalence of oseltamivir suspension in healthy Chinese subjects

Objective This study was conducted to evaluate the bioequivalence, pharmacokinetic profiles, and safety of a generic oseltamivir suspension compared with the branded reference product (Tamiflu®) under both fasting and fed conditions in healthy adult volunteers(HVs). Methods Two separate randomized, open-label, single-dose, two-period crossover studies were conducted under fasting (n = 50) and fed (n = 36) conditions. In each study, HVs were randomly assigned in a 1:1 ratio to receive either the test followed by the reference formulation (T-R) or the reverse sequence (R-T), with a 7-day washout period between doses. All participants received 0.075 g dose of oseltamivir suspension. Plasma concentrations of oseltamivir and its metabolite oseltamivir carboxylate were quantified using high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Pharmacokinetic parameters were derived via noncompartmental analysis, and bioequivalence was evaluated accordingly. Results A total of 82 healthy volunteers (HVs) were enrolled in the study. Under fasting conditions, the maximum plasma concentration (C _max , mean ± SD) was 54.7 ± 19.7 ng/mL at 1.50 hours for sponsor T, and 53.1 ± 18.0 ng/mL at 1.12 hours for sponsor R. In fed subjects, C _max was 39.0 ± 12.4 ng/mL at 1.66 hours for sponsor T, and 36.1 ± 13.3 ng/mL at 1.66 hours for sponsor R. All 90% confidence intervals (CIs) for C _max , AUC _0 − t , and AUC _0−∞ were within the bioequivalence bounds (80–125%) both fasting and fed studies. Conclusion Oseltamivir suspension was well-tolerated with a favorable safety profile. No serious adverse events (SAEs) or AEs leading to study discontinuation were reported under either fasting or fed conditions. Bioequivalence was established under both nutritional states, supporting biosimilarity between formulations. Together with the favorable safety outcomes, these results support the therapeutic equivalence of the test formulation to the reference formulation.