Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Etoricoxib is a selective cyclooxygenase-2 inhibitor widely used for the treatment of pain and inflammatory conditions. However, comparative pharmacokinetic and bioequivalence data for locally manufactured etoricoxib formulations in the Pakistani population remain limited. Objective: This study aimed to evaluate the pharmacokinetics and bioequivalence of a locally manufactured etoricoxib tablet compared with the innovator product in healthy Pakistani volunteers, with supportive assessment using physiologically based pharmacokinetic (PBPK) modeling. Methods: Comparative in-vitro dissolution studies were conducted in buffer media of pH 1.2, 4.5 and 6.8 and evaluated using similarity factor (f?) analysis. A randomized, open-label, two-treatment, two-period crossover bioequivalence study was performed in healthy male volunteers under fasting conditions. Subjects received a single oral dose of 120 mg Etoricoxib (ETO) as either the test product (Etoxib®) or the reference product (Arcoxia®), with a 14-day washout period. Plasma concentrations were quantified using a validated HPLC-UV method and pharmacokinetic parameters were estimated using non-compartmental analysis. PBPK modeling of the test product was conducted using GastroPlus® to assess model predictability. Results: The test and reference products exhibited similar dissolution profiles across all media, with f? values indicating similarity. The geometric mean ratios (90% confidence intervals) of the test to reference product for Cmax, AUC0–t and AUC0–? were 0.946 (0.8855–1.0135), 0.923 (0.8705–0.9795) and 0.960 (0.8955–1.0255), respectively, all within the regulatory bioequivalence acceptance range. PBPK model predictions for key pharmacokinetic parameters were within an acceptable fold-error range (?2) compared with observed data. Conclusion: The study demonstrated comparable systemic exposure and confirmed bioequivalence between the locally manufactured and innovator etoricoxib formulations in the Pakistani population. PBPK modeling provided supportive evidence of formulation similarity and model adequacy.