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Neglecting plasma protein binding in COVID-19 patients leads to a wrong interpretation of lopinavir overexposure

dc.rights.licenseopenen_US
dc.contributor.authorSTANKE-LABESQUE, Francoise
dc.contributor.authorCONCORDET, Didier
dc.contributor.authorDJERADA, Zoubir
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBOUCHET, Stephane
dc.contributor.authorSOLAS, Caroline
dc.contributor.authorMERIGLIER, Etienne
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBONNET, Fabrice
dc.contributor.authorMOURVILLIER, Bruno
dc.contributor.authorRUIZ, Stephanie
dc.contributor.authorMARTIN-BLONDEL, Guillaume
dc.contributor.authorEPAULARD, Olivier
dc.contributor.authorSCHWEBEL, Carole
dc.contributor.authorGAUTIER-VEYRET, Elodie
dc.contributor.authorGANDIA, Peggy
dc.date.accessioned2021-04-07T10:46:44Z
dc.date.available2021-04-07T10:46:44Z
dc.date.issued2021-02
dc.identifier.issn0009-9236en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26884
dc.description.abstractEnBoffito et al. recalled the critical importance to correctly interpret protein binding. Changes of lopinavir pharmacokinetics in COVID-19 are a perfect illustration. Indeed, several studies described that total lopinavir plasma concentrations were considerably higher in severe COVID-19 patients than those reported in HIV patients. These findings have led to a reduction of the dose of lopinavir in some patients, hypothetizing an inhibitory effect of inflammation on lopinavir metabolism. Unfortunately, changes in plasma protein binding were never investigated. We performed a retrospective cohort study. Data were collected from the medical records of patients hospitalized for COVID-19 treated with lopinavir/ritonavir in intensive care units or infectious disease departments of Toulouse university hospital (France). Total and unbound concentrations of lopinavir, C reactive protein, albumin and alpha-1-acid glycoprotein (AAG) levels were measured during routine care on the same samples. In COVID-19 patients, increased total lopinavir concentration is the result of an increased AAG-bound lopinavir concentration whereas the unbound concentration remains constant, and insufficient to reduce the SARS-CoV-2 viral load. Although international guidelines have recently recommended against using lopinavir/ritonavir to treat severe COVID-19, the description of lopinavir pharmacokinetics changes in COVID-19 is a textbook case of the high risk of misinterpretation of a total drug exposure when changes in protein binding are not taken into consideration.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.title.enNeglecting plasma protein binding in COVID-19 patients leads to a wrong interpretation of lopinavir overexposure
dc.title.alternativeClin Pharmacol Theren_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1002/cpt.2196en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed33547636en_US
bordeaux.journalClinical Pharmacology and Therapeuticsen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERM
bordeaux.teamPharmacoEpi-Drugsen_US
bordeaux.teamMORPH3Eusen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03191652
hal.version1
hal.date.transferred2021-04-07T10:46:48Z
hal.audienceInternationale
hal.exporttrue
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