Journal Article

Favipiravir pharmacokinetics in Ebola-Infected patients of the JIKI trial reveals concentrations lower than targeted

Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA) ; Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM), Raoul, Hervé, Pastorino, Boris, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections [CIRI] (UBIVE) ; Centre International de Recherche en Infectiologie (CIRI) ; École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National

2017

Overview

n 2014–2015, the JIKI trial was conducted in Guinea to test favipiravir tolerance and efficacy in patients with Ebola virus disease (EDV). The main results of the trial were previously published without drug concentrations which were not available at the time of publication. The purpose of this study was to report favipiravir concentrations achieved in participants in the JIKI trial and to compare them with the targeted concentrations. We analyzed drug concentrations obtained at Day-2 and Day-4 and compared them to the targeted concentrations. At Day-2, favipiravir concentrations were significantly below but still close to the targeted concentration. At Day-4, a significant and unanticipated drop of concentrations as compared to Day-2 was observed. The origin of the lower-than-targeted concentrations and the unexpected drop could be due to severe sepsis conditions and/or to intrinsic properties of favipiravir metabolism. No significant correlation was found between the drug exposure and the virological response, indicating that it is possible that the favipiravir concentrations in the JIKI trial were not sufficient to strongly inhibit the viral replication. These findings suggest the necessity of performing dose-ranging studies with high doses of favipiravir in healthy volunteers to inform any further development of favipiravir for treatment of EVD.

• Publisher: Public Library of Science,CCSD,Public Library of Science (PLoS)
• Subject: Adolescent / Adult / Aged / Amides / Amides - administration & dosage / Amides - pharmacokinetics / Antiviral Agents / Antiviral Agents - administration & dosage / Antiviral Agents - pharmacokinetics / Biology and Life Sciences / Child / Child, Preschool / Drug dosages / Drug therapy / Ebola hemorrhagic fever / Ebola virus / Ebolavirus / Ebolavirus - drug effects / Ebolavirus - physiology / Female / Guinea / Health care / Hemorrhagic Fever, Ebola / Hemorrhagic Fever, Ebola - drug therapy / Hemorrhagic Fever, Ebola - virology / Humans / Life Sciences / Male / Medicine and Health Sciences / Metabolism / Microbiology and Parasitology / Middle Aged / Patient outcomes / Patients / Pharmacokinetics / Public health / Pyrazines / Pyrazines - administration & dosage / Pyrazines - pharmacokinetics / Sepsis / Tropical diseases / Virology / Young Adult