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dc.rights.licenseopenen_US
dc.contributor.authorSALAM, Alex P.
hal.structure.identifierBordeaux population health [BPH]
hal.structure.identifierGlobal Health in the Global South [GHiGS]
dc.contributor.authorDUVIGNAUD, Alexandre
hal.structure.identifierBordeaux population health [BPH]
hal.structure.identifierGlobal Health in the Global South [GHiGS]
dc.contributor.authorJASPARD, Marie
hal.structure.identifierBordeaux population health [BPH]
hal.structure.identifierGlobal Health in the Global South [GHiGS]
dc.contributor.authorMALVY, Denis
ORCID: 0000-0003-1948-9355
IDREF: 148480993
dc.contributor.authorCARROLL, Miles
dc.contributor.authorTARNING, Joel
dc.contributor.authorOLLIARO, Piero L.
dc.contributor.authorHORBY, Peter W.
dc.date.accessioned2022-04-19T08:52:46Z
dc.date.available2022-04-19T08:52:46Z
dc.date.issued2022-03
dc.identifier.issn1935-2735 (Electronic) 1935-2727 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/136654
dc.description.abstractEnRibavirin is currently the standard of care for treating Lassa fever. However, the human clinical trial data supporting its use suffer from several serious flaws that render the results and conclusions unreliable. We performed a systematic review of available pre-clinical data and human pharmacokinetic data on ribavirin in Lassa. In in-vitro studies, the EC50 of ribavirin ranged from 0.6 μg/ml to 21.72 μg/ml and the EC90 ranged from 1.5 μg/ml to 29 μg/ml. The mean EC50 was 7 μg/ml and the mean EC90 was 15 μg/ml. Human PK data in patients with Lassa fever was sparse and did not allow for estimation of concentration profiles or pharmacokinetic parameters. Pharmacokinetic modelling based on healthy human data suggests that the concentration profiles of current ribavirin regimes only exceed the mean EC50 for less than 20% of the time and the mean EC90 for less than 10% of the time, raising the possibility that the current ribavirin regimens in clinical use are unlikely to reliably achieve serum concentrations required to inhibit Lassa virus replication. The results of this review highlight serious issues with the evidence, which, by today standards, would be unlikely to support the transition of ribavirin from pre-clinical studies to human clinical trials. Additional pre-clinical studies are needed before embarking on expensive and challenging clinical trials of ribavirin in Lassa fever.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enRibavarin for treating Lassa fever: A systematic review of pre-clinical studies and implications for human dosing
dc.typeArticle de revueen_US
dc.identifier.doi10.1371/journal.pntd.0010289en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed35353804en_US
bordeaux.journalPLoS Neglected Tropical Diseasesen_US
bordeaux.volume16en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue3en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamGHIGS_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03644433
hal.version1
hal.date.transferred2022-04-19T08:52:48Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS%20Neglected%20Tropical%20Diseases&rft.date=2022-03&rft.volume=16&rft.issue=3&rft.eissn=1935-2735%20(Electronic)%201935-2727%20(Linking)&rft.issn=1935-2735%20(Electronic)%201935-2727%20(Linking)&rft.au=SALAM,%20Alex%20P.&DUVIGNAUD,%20Alexandre&JASPARD,%20Marie&MALVY,%20Denis&CARROLL,%20Miles&rft.genre=article


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