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We developed a population pharmacokinetic and pharmacodynamic (PopPK\/PD) model of DEX anti\u2010inflammatory effects in COVID\u201019 and provide simulations comparing the expected efficacy of four dosing regimens of DEX. Nonlinear mixed\u2010effects modeling and simulations were performed using Monolix Suite version 2021R1 (Lixoft, France). Published data for DEX PK in patients with COVID\u201019 exhibited moderate variability with a clearance of about half that in healthy adults. No accumulation of the drug was expected even with daily oral doses of 12\u2009mg. Indirect effect models of DEX inhibition of TNF\u03b1, IL\u20106, and CRP plasma concentrations were enacted and simulations performed for DEX given at 1.5, 3, 6, and 12\u2009mg daily for 10\u2009days. The numbers of individuals that achieved specified reductions in inflammatory biomarkers were compared among the treatment groups. The simulations indicate the need for 6 or 12\u2009mg daily doses of DEX for 10\u2009days for simultaneous reductions in TNF\u03b1, IL\u20106, and CRP. Possibly beneficial is DEX given at a dose of 12\u2009mg compared to 6\u2009mg. The PopPK\/PD model may be useful in the assessment of other anti\u2010inflammatory compounds as well as drug combinations in the treatment of cytokine storms.<\/jats:p>","DOI":"10.1111\/cts.13577","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T04:09:03Z","timestamp":1688098143000},"page":"1667-1679","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Anti\u2010inflammatory effects of dexamethasone in <scp>COVID<\/scp>\u201019 patients: Translational population <scp>PK<\/scp>\/<scp>PD<\/scp> modeling and simulation"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-9709","authenticated-orcid":false,"given":"Artur","family":"\u015awierczek","sequence":"first","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy Jagiellonian University Medical College  Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Jusko","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences State University of New York at Buffalo  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,5]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"33","article-title":"SARS, MERS and COVID\u201019: clinical manifestations and organ\u2010system complications: a mini review","volume":"78","author":"Harb JG","year":"2020","journal-title":"Pathog Dis"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02049-2020"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.14462"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-020-05190-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.01.006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2021.1918103"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8874339"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2021.e06187"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2217\/fvl-2021-0249"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1586\/ers.10.71"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270003258651"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(96)00385-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021436"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.18295"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-021-06573-1"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-021-00341-0"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14595"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1051-9"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-041471"},{"key":"e_1_2_9_21_1","first-page":"105","article-title":"Dexamethasone metabolism by human liver in vitro. 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