Contributors: Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)); Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM); Programme PAC-CI; ANRS France Recherche Nord & sud Sida-hiv hépatites; Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA); Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA); Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); 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 Claude Bernard Lyon 1 (UCBL); Université de Lyon-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 Claude Bernard Lyon 1 (UCBL); Université de Lyon-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)-Institut Pasteur Paris (IP); Emergence des Pathologies Virales (EPV); Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM); Aix Marseille Université (AMU); Médecins Sans Frontières Belgique; The Alliance for International Medical Action Dakar, Sénégal (ONG ALIMA); Université Catholique de Louvain = Catholic University of Louvain (UCL); Laboratoire des Fièvres Hémorragiques en Guinée; Université Gamal Abdel Nasser de Conakry; Laboratoire P4 - Jean Mérieux; Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM); Institut National de la Santé et de la Recherche Médicale (INSERM); The JIKI trial was supported by grants from the French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France, http://www.anrs.fr/), the French Institute for Health Research (Inserm, Paris, France, http://www.inserm.fr/) and the European Commission (EU Horizon 2020 programme, grant N° 666092 - REACTION, http://ec.europa.eu/programmes/horizon2020/).; ANR-10-INBS-0006,HIDDEN,Extension de l'infrastructure de recherche dédiée aux maladies hautement infectieuses(2010); European Project: 666092,H2020,H2020-Adhoc-2014-20,REACTION(2014)
نبذة مختصرة : International audience ; 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.
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