Bioequivalence Study of Two Formulations of Cefixime

Abstract

Cefixime is a broad-spectrum oral antibiotic used for treating a wide variety of bacterial infections. Study Objective: The objective of this study was to find out whether bioequivalence study of Cefixime 200 mg, Profim® capsule manufactured by PT Promedrahardjo Farmasi Industri in comparison with Cefixime 100 mg, Cefspan® capsule manufactured by PT Dankos Farma, For PT Kalbe Farma Tbk, under license by Astellas Pharma Inc., Osaka – Japan. Methods: The study was conducted using an open-label, randomized, single-dose, two-periods, two-treatments, crossover study under fasting conditions with 8 (eight) days washed-out period between each period. According to the random design, a single oral dose of the test drug or reference drug was administered to 30 healthy male subjects after overnight fasting. The number of subjects who finished the study was twenty-eight (28) healthy male subjects. Serial plasma samples were obtained over a 32 hours period. Plasma concentrations of the drug were determined by LC-MS/MS method. From the Cefixime concentration vs. time curves, the following pharmacokinetic parameters were obtained: AUC0-32h, AUC0-∞, and Cmax, while the statistical interval proposed was 80.00 - 125.00% for AUC0-32h 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 Profim® (BN: B051A21P-1)/ reference drug, Cefspan® (BN: KCEFB00038) ratio were as follows: AUC0-32h: 105.86 (95.41 - 117.44) with CV Intra Subjects was 22.72% and Cmax: 105.63 (95.33 - 117.03) with CV Intra Subjects was 22.43 %. Whilst TMAX of the test drug Profim® (BN: B051A21P-1)/ reference drug, Cefspan® (BN: KCEFB00038) were respectively 4.50 (3.50 – 6.00) h and 4.50 (3.00 – 6.00) h; mean T1/2 were respectively 4.18 ± 0.78 h and 4.14 ± 0.56 h; and mean Slope were respectively (-0.17) ± 0.03 h and (-0.17) ± 0.02 h. There is no adverse event that occurred during this study. Conclusion: The present study demonstrated that the evaluated test drug Profim® (BN: B051A21P-1) were bioequivalence in term of both rate and extent of absorption to the reference drug Cefspan® (BN: KCEFB00038).