Population pharmacokinetics of lopinavir/ritonavir in Covid-19 patients
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PHARMACOKINETICS AND DISPOSITION
Population pharmacokinetics of lopinavir/ritonavir in Covid-19 patients Jean Claude Alvarez 1,2 & Pierre Moine 3 & Benjamin Davido 4 & Isabelle Etting 1 & Djillali Annane 3 & Islam Amine Larabi 1 & Nicolas Simon 5 & on behalf of the Garches COVID-19 Collaborative GroupAmbrosi, Xavier, Amthor, Suzanne, Bounab, Rania, Chentouh, Ryme, Clair, Bernard, Fayssoil, Abdallah, Friedman, Diane, Heming, Nicholas, Maxime, Virginie, Niel Duriez, Myriam, Orlikowski, David, Santi, Francesca, Villart, Maryvonne, Michelon Hugues, Abbar, Baptiste, Dray, Juliah, Tamayo, Juan, Pascault, Alice, Zini; Justine, Bennington, Steven, Moucachen, Myriam, Gay, Pierre, Luxman, Majistor, Kochbati, Elias, Martinez, Valéria, Guichard, Léa, Trabelsi, Chawki, Boutros, Marie, Schitter, Sebastien, Meuleye, Simone, Reysz, Suzanne, Khiter, Hakim, Dosne Blachier, Brigitte, Bron, Anne Lyse, Defouchecour, Etiennette, Hamon Pietrin, Damien, Coester, Denys, Bergounioux Jean, Omar, Amal, Guillon, Maud, Amthor, Helge, Prigent, Helene, Lofaso, Frédéric, Denys Pierre, Bensmail, Djamel, Joussain, Charles, Malot, Claire, Lansaman, Thibaut, Leotard, Antoine, Le Liepvre, Hélène, Rech, Celia, Paquereau, Julie, Kagane, Lauren, Levy, Jonathan, Chkron, Elsa, Angioni, Florence, Karabulut, Céline, Lemoine, Jérôme, Vibert, Julien, Trystram, Noémie, Christian Perronne, Véronique Perronne, Aurélien Dinh, Pierre de Truchis, Soline Simeon, Bessis Simon, Morgan Matt, Hélène Mascitti, Stéphanie Landowski, Pascal Crenn, Aurélie Le Gal, Aymeric Lanore, Julia Nguyen Van Thang, Louis Jacob, Nicolas Kiavue, Marc Hobeika, Jean Louis Gaillard, Jean Louis Hermann, Martin Rottman, Anne Laure Roux, Marie-Anne Welti, Elyanne Gault, Christine Lawrence Received: 22 June 2020 / Accepted: 7 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Objective To develop a population pharmacokinetic model for lopinavir boosted by ritonavir in coronavirus disease 2019 (Covid-19) patients. Methods Concentrations of lopinavir/ritonavir were assayed by an accredited LC-MS/MS method. The population pharmacokinetics of lopinavir was described using non-linear mixed-effects modeling (NONMEM version 7.4). After determination of the base model that better described the data set, the influence of covariates (age, body weight, height, body mass index (BMI), gender, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), C reactive protein (CRP), and trough ritonavir concentrations) was tested on the model. Results From 13 hospitalized patients (4 females, 9 males, age = 64 ± 16 years), 70 lopinavir/ritonavir plasma concentrations were available for analysis. The data were best described by a one-compartment model with a first-order input (KA). Among the covariates tested on the PK parameters, only the ritonavir trough concentrations had a significant effect on CL/F and improved Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00228-020-03020-w) contains supplementary material, which
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