Bioequivalence Study of Salbutamol 400 mg Tablet in Healthy Indonesian Volunteers by Liquid Chromatography Tandem with Mass Spectrometry

Abstract

This study objective was to determine the bioequivalence of Salbutamol 4 mg Tablet manufactured by PT Kimia Farma Tbk compared to Ventolin® 2x2 mg Tablet manufactured by Glaxo Wellcome Indonesia, in healthy Indonesian volunteer. The pharmacokinetic parameters calculated in this study are AUC0-24, AUC0-inf, Cmax, Tmax, and T1/2. The study was conducted in a randomized, single-dose, open-label, two-way crossover design (2 treatments, 2 periods, and 2 sequences) under fasting state with 7 (seven) days washed-out period. The number of subjects who participated in the study were 24 volunteers ((12 males and 12 females). The participants were provided with an overview of the study and signed the informed consent form. The study participants underwent a minimum 8-hour fasting period prior to receiving both the test drug and the reference drug, and blood samples were collected at 14 specified time points: 0 hours (before drug administration), minutes-20, minutes-40, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours after drug administration. Plasma concentrations of the drug were determined by LCMS/MS method. The acceptance criteria for the bioequivalence test are 80.00 - 125.00% for AUC0-t and Cmax with 90% Confidence Interval (CI) with α = 5.00%. The mean SD value of AUC0-24, AUC0-inf, Cmax, Tmax, and T1/2 respectively for test drug is 84.49 ±18.99 ng.mL-1.hour; 89.66 ±21.29 ng.mL-1.hour; 13.85 ±4.25 ng/mL; 2.00 ±0.71 hour and 5.08 ±1.27 hour. The mean SD values of AUC0-24, AUC0-inf, Cmax, Tmax, and C1/2 respectively for reference drug are 88.81 ±26.50 ng.mL-1.jam; 93.78 ±27.97 ng.mL-1.jam; 13.39 ±5.39 ng/mL; 2.63 ±1.45 hour and 5.03 ±1.16 hour. Meanwhile, the geometric mean ratio of test drug to reference drug (90% confidence interval) is 96.35% (90.55- 102.53%) for AUC0-24 and 105.39% (93.62-118.65%) for Cmax. Based on the AUC0-24 and Cmax values, Salbutamol 4 mg Tablet manufactured by PT Kimia Farma Tbk is bioequivalent to Ventolin® 2x2 mg Tablet manufactured by Glaxo Wellcome Indonesia.