Does the Ethnic Difference Affect the Pharmacokinetics of Favipiravir? A Pharmacokinetic Study in Healthy EgyptianVolunteers and Development of Level C In-vitro In-vivo Correlation

Abstract

Abstract Background and Objective Favipiravir is an antiviral drug used to treat influenza. It is also being investigated for the treatment of a variety of other viral diseases, including SARS-CoV-2. Its pharmacokinetic profile varies depending on ethnic group. The present research examines the pharmacokinetic (Pk) features of favipiravir in healthy male Egyptian volunteers. Another goal of this research is to determine the optimum dissolution testing conditions for immediate release (IR) tablets.Methods In vitro dissolution testing was investigated for favipiravir tablet, Avigan® 200 mg tablets, in three different pH media. The pharmacokinetic (Pk) features of favipiravir were examined in healthy male Egyptian volunteers. A newly developed and validated LC-MS/MS method was used to analyze real plasma samples of the healthy volunteers. Level C in vitro in vivo correlation (IVIVC) was developed to set the optimum dissolution medium to achieve accurate dissolution profile for favipiravir (IR) tablets.Results In vitro dissolution results revealed significant difference among the three different dissolution media. The Pk parameters of twenty-seven human subjects showed mean value of Cp max of 5966.45 ng/mL at median tmax of 0.75 h with AUC0-∞ equals 13325.54 ng.h/mL, showing half-life of 1.25 h. AUC0-t vs. % dissolved was used to develop level C IVIVC for favipiravir (IR) tablets.Conclusions When compared to American and Caucasian volunteers, Egyptian participants had comparable Pk values, however they were considerably different from Japanese subjects. Phosphate buffer medium (pH 6.8) was found to be the optimum dissolution medium for in vitro dissolution testing for Favipiravir IR tablets.