Bioequivalence Profile Prediction of Favipiravir Using Everted Gut Sac

Abstract

 Favipiravir is one of broad-spectrum antiviral drugs approved for the treatment of the influenza virus and SARS-CoV-2, it is known to have inhibitory activity towards RNA dependent RNA polymerase (RdRp). The permeability of Favipiravir in tablet form was conducted using an everted gut sac model for evaluating ex vivo drug absorption as an approach before starting the Pivotal Bioequivalence Study. One formulated Favipiravir tablet 200 mg by Kimia Farma was selected.
Avigan® 200 mg manufactured by Fujifilm Toyama Chemical Co. Ltd was used as reference. In vitro comparative dissolution testing and absorption experiments were conducted. Ex Vivo absorption experiment was developed by using an everted gut sac from male rats intestinal. Absorption rate was used to demonstrate drug molecule intestinal permeability. The rate between test and reference drug was evaluated using a paired student T-test. The resulting data is used to make the bioequivalence study decision. Open-label, randomized, single-dose, two-period, two-sequences, crossover bioequivalence study was carried out under fasting conditions which included 30 healthy adult male and female subjects. Bioequivalence pharmacokinetics parameters assessed in this study were Cmax and AUC0-t. Similarity factor (f2) of comparative dissolution testing between test and reference drug was more than 50 in three mediums (pH 1.2; pH 4.5; pH 6.8). Absorption rates of test and reference drugs were not significantly different (t =0.6683 (< t critical 2.571). Favipiravir tablets produced by Kimia Farma have similar absorption rates compared to the reference drugs. The Bioequivalence study result was satisfactory. The geometric mean ratios of the test drug to the reference drug (90% CI) were 101.27% (96.89-105.86) for AUC0-t and 101.22% (96.80-105.84) for Cmax. All values were within the accepted bioequivalence range of 80.00-125.00% for both AUC0-t and Cmax.