{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T06:44:58Z","timestamp":1773470698750,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:p>Janus kinase (JAK) inhibitors baricitinib and tofacitinib are recommended by the US National Institutes of Health as immunomodulatory drugs for coronavirus disease 2019 (COVID\u201019) treatment. In addition, baricitinib has recently received Emergency Use Authorization from the US Food and Drug Administration, although the instruction provided dosing information only for adults. Geriatrics with organ dysfunction are one of the most vulnerable cohorts when combating the pandemic. The aim of the present work was to evaluate current dosing strategies of baricitinib and tofacitinib for potential COVID\u201019 treatment for White and Chinese geriatric patients with chronic renal impairment. An established physiologically\u2010based pharmacokinetic (PBPK) modeling framework for age\u2010dependent simulations was utilized. PBPK drug models adopted from literature were first verified. Several population models representing different age groups, ethnicities, and stages of renal impairment were used for prospective simulations. Notwithstanding the increase in systemic exposure of both drugs resulting from renal dysfunction was more pronounced for geriatrics than general White populations, our simulations confirmed their current dosage adjustments based on renal functions are broadly adequate. The exception being White older subjects with mild renal impairment where current recommendation of 4\u00a0mg baricitinib yielded a 2.31\u2010fold increase in systemic exposure, and reduction to 2\u00a0mg could mitigate the potential risk to an acceptable 1.15\u2010fold. Comparable relationships between systemic exposure and renal dysfunction were observed for both drugs in the Chinese population. In summary, PBPK modeling of both JAK inhibitors supports the rational and prudent dose adjustments of these COVID\u201019 therapeutics among adult patients of different age groups and renal functions.<\/jats:p>","DOI":"10.1002\/cpt.2600","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T07:54:54Z","timestamp":1649145294000},"page":"291-296","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Physiologically\u2010Based Pharmacokinetic Modelling to Investigate Baricitinib and Tofacitinib Dosing Recommendations for COVID\u201019 in Geriatrics"],"prefix":"10.1111","volume":"112","author":[{"given":"Ziteng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy Faculty of Science National University of Singapore  Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric Chun Yong","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Faculty of Science National University of Singapore  Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2020.108393"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30132-8"},{"key":"e_1_2_9_4_1","unstructured":"National Institutes of Health.Coronavirus disease 2019 (COVID\u201019) treatment guidelines<https:\/\/www.covid19treatmentguidelines.nih.gov\/> (2021)."},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2020.06.007"},{"key":"e_1_2_9_6_1","unstructured":"U.S. Food and Drug Administration.Baricitinib EUA letter of authorization<https:\/\/www.fda.gov\/media\/143822\/download> (2021)."},{"key":"e_1_2_9_7_1","unstructured":"National Centre for Infectious Diseases.Treatment guidelines for COVID\u201019<https:\/\/www.ncid.sg\/Health\u2010Professionals\/Diseases\u2010and\u2010Conditions\/Documents\/Treatment%20Guidelines%20for%20COVID\u201019%20v7%20Final%20%20%2828\u20107\u20102021%29.pdf> (2021)."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2016.1241237"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30264-3"},{"key":"e_1_2_9_10_1","unstructured":"U.S. Food and Drug Administration.XELJANZ prescribing information<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/203214s018lbl.pdf>."},{"key":"e_1_2_9_11_1","unstructured":"U.S. Food and Drug Administration.OLUMIANT prescribing information<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/207924s002lbl.pdf>."},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2452"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557\u2010021\u201007266\u2010z"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.01.044"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12486"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1679"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14609"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.750"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.868"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.178"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.202"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.354"},{"key":"e_1_2_9_23_1","unstructured":"European Medicines Agency.Xeljanz product information<https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/xeljanz>."},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2020.5084"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0709-7"}],"container-title":["Clinical Pharmacology &amp; 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