Bioequivalence Study of Etoricoxib 120 mg in Healthy Subjects

Abstract

Etoricoxib is an oral selective cyclo-oxygenase-2 (COX-2) inhibitor with anti-inflammatory and antirheumatic properties belonging to the group of NSAIDs. Study Objective: The objective of this study was to investigate the bioequivalence study of Etoricoxib, Tricox® 120 mg film coated caplet manufactured by PT Guardian Pharmatama for PT Nulab Pharmaceutical Indonesia in comparison with Etoricoxib 120 mg, Arcoxia® film coated tablet manufactured by Frosst Iberica, S.A., Spain, registered and packed by PT Merck Sharp Dohme Pharma Tbk Pasuruan, East Java. Indonesia. Methods: The study was conducted using an open-label, randomized, single-dose, two-periods, two-treatment, crossover study under fasting for 10 hours with 7 (seven) days washed-out period between each period. A single oral dose of the test drug or reference drug was administered to 16 healthy male subjects. The number of subjects who finished the study was fourteen (14) healthy male subjects. Serial plasma samples were obtained over a 72 hours period. Plasma concentrations of the drug were determined by LC-MS/MS method. From the Etoricoxib concentration vs. time curves, the following pharmacokinetic parameters were obtained: AUC0-72h, AUC0-∞, and Cmax, while the statistical interval proposed was 80.00 - 125.00% for AUC0-72h and Cmax with 90% Confidence Interval (CI) with α = 5.00%. The estimation of Tmax and T1/2 in the bioequivalence study was based on a nonparametric statistical procedure on the original data using Wilcoxon Sign Test. Results: The main pharmacokinetic parameters of the test drug Tricox® (BN: T200909) compared to reference drug, Arcoxia® (BN: T015857) were calculated based on geometric mean ratio and 90% confidence interval (CI). The results for AUC0-72h and Cmax were 91.97% (87.50% – 96.66%) and 96.98% (88.41% – 106.36%) respectively, with intra-subject variability (%CV) were 13.56% for AUC0-72h and 7.28% for Cmax. Hence, the number of 14 (fourteen) subjects has adequate number for required power of study. Conclusion: The study demonstrated that the test drug Tricox® (BN: T200909) manufactured by PT Guardian Pharmatama for PT Nulab Pharmaceutical Indonesia bioequivalence in term of both rate and extent of absorption to the reference drug Arcoxia® (BN: T015857) manufactured by Frosst Iberica, S.A., Spain, registered and packed by PT Merck Sharp Dohme Pharma Tbk Pasuruan, East Java. Indonesia.