{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T15:17:43Z","timestamp":1785943063345,"version":"3.56.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Line 1-Ricerca Corrente \u2018Infezioni Emergenti e Riemergenti\u2019"},{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Remdesivir is the first antiviral drug against SARS-CoV-2 approved for use in COVID-19 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To study the pharmacokinetic inter-individual variability of remdesivir and its main metabolite GS-441524 in a real-world setting of COVID-19 inpatients and to identify possible associations with different demographic\/biochemical variables.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Inpatients affected by SARS-CoV-2 infections, undergoing standard-dose remdesivir treatment, were prospectively enrolled. Blood samples were collected on day 4, immediately after (C0) and at 1\u2005h (C1) and 24\u2005h (C24) after infusion. Remdesivir and GS-441524 concentrations were measured using a validated UHPLC-MS\/MS method and the AUC0\u201324 was calculated. At baseline, COVID-19 severity (ICU or no ICU), sex, age, BMI and renal and liver functions were assessed. Transaminases and estimated glomerular filtration rate (e-GFR) were also evaluated during treatment. Linear regression, logistic regression and multiple linear regression tests were used for statistical comparisons of pharmacokinetic parameters and variables.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eighty-five patients were included. The mean (CV%) values of remdesivir were: C0 2091 (99.1%) ng\/mL, C1 139.7 (272.4%) ng\/mL and AUC0\u201324 2791 (175.7%) ng\u00b7h\/mL. The mean (CV%) values of GS-441524 were: C0 90.2 (49.5%) ng\/mL, C1 104.9 (46.6%) ng\/mL, C24 58.4 (66.9) ng\/mL and AUC0\u201324 1976 (52.6%) ng\u00b7h\/mL. The multiple regression analysis showed that age (P\u200a&amp;lt;\u200a0.05) and e-GFR (P\u200a&amp;lt;\u200a0.01) were independent predictors of GS-441524 plasma exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results showed a high interpatient variability of remdesivir and GS-441524 likely due to both age and renal function in COVID-19 inpatients. Further research is required to understand whether the pharmacokinetics of remdesivir and its metabolites may influence drug-related efficacy or toxic effect.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkac234","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T12:34:53Z","timestamp":1658147693000},"page":"2683-2687","source":"Crossref","is-referenced-by-count":5,"title":["Interpatient variability in the pharmacokinetics of remdesivir and its main metabolite GS-441524 in treated COVID-19 subjects"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3107-7441","authenticated-orcid":false,"given":"Massimo","family":"Tempestilli","sequence":"first","affiliation":[{"name":"National Institute for Infectious Diseases \u2018Lazzaro Spallanzani\u2019 IRCCS , 00149, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Ascoli Bartoli","sequence":"additional","affiliation":[{"name":"National Institute for Infectious Diseases \u2018Lazzaro Spallanzani\u2019 IRCCS , 00149, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Benvenuto","sequence":"additional","affiliation":[{"name":"Infectious Disease Unit, Tor Vergata University Hospital , 00133, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia Valeria","family":"Stazi","sequence":"additional","affiliation":[{"name":"National Institute for Infectious Diseases \u2018Lazzaro Spallanzani\u2019 IRCCS , 00149, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Marchioni","sequence":"additional","affiliation":[{"name":"National Institute for Infectious Diseases \u2018Lazzaro Spallanzani\u2019 IRCCS , 00149, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Nicastri","sequence":"additional","affiliation":[{"name":"National Institute for Infectious Diseases \u2018Lazzaro Spallanzani\u2019 IRCCS , 00149, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5252-0927","authenticated-orcid":false,"given":"Chiara","family":"Agrati","sequence":"additional","affiliation":[{"name":"National Institute for Infectious Diseases \u2018Lazzaro Spallanzani\u2019 IRCCS , 00149, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"2022093019444819800_dkac234-B1","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1126\/science.367.6485.1412","article-title":"Race to find COVID-19 treatments 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