Pharmacokinetics and Bioequivalence Study of Two Formulations of Favipiravir 200 mg Film-Coated Tablet in Healthy Indonesian Volunteers

Abstract

This study objective was to determine the bioequivalence of two Favipiravir 200 mg Film-Coated Tablet formulations (test and reference formulation). This study was an open label, randomized, single-dose, two-period, two-sequences, crossover study under fasting condition which included 30 healthy Indonesian volunteers. The participants were informed about this study and provided written consent. Subjects were fasted for at least 8 hours before receiving the test and reference drugs. Blood samples were collected at 17 different time points, including prior to drug administration and at various intervals up to 24 hours after drug administration. Favipiravir plasma concentrations were determined using an LC-MS/MS method. The main pharmacokinetic parameters calculated, namely the area under the plasma concentration-time curve (AUC0-t) and maximum plasma concentration (Cmax), are expected to demonstrate bioequivalence. The bioequivalence acceptance range is 80.00%- 125.00% for the 90% confidence interval of the geometric least square means ratio for AUC0-t and Cmax. The mean ± SD values for AUC0-24 and Cmax of the test drug were 15,756.77± 4,773.47 ng·mL-1·hr and 7,237.49 ± 1,441.07 ng/mL, respectively. The mean ± SD values for AUC0-24 and Cmax of the Reference drug were 15,491.62 ± 4,288.43 ng·mL-1·hr and 7,218.51 ± 1,896.11 ng/mL, respectively. The geometric mean ratio of the test drug to the Reference drug (90% CI) was 101.27% (96.89-105.86) for AUC0-24 and 101.22% (96.80-105.84) for Cmax. The results of this study in healthy indonesian volunteers indicate that Favipiravir 200 mg Film-Coated Tablet manufactured by PT Kimia Farma Tbk are bioequivalent to the reference product — Avigan® 200 mg mg Film-Coated Tablet manufactured by Fujifilm Toyama Chemical Co., Ltd.