{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:11:17Z","timestamp":1777900277259,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R43GM133232"],"award-info":[{"award-number":["R43GM133232"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Numer Methods Biomed Eng"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hydroxychloroquine (HCQ) is commonly used in the treatment of malaria and rheumatic diseases. Recently it has also been identified as possible therapeutic option in combating COVID\u201019. However, the use of HCQ is known to induce cytotoxicity. In 2020, we developed a multiscale absorption and transit (MAT) toolkit to simulate the dissolution, transport, absorption, distribution, metabolism, and elimination of orally administered drugs in the human GIT at multiple levels. MAT was constructed by integrating the spatially accurate first\u2010principles driven high\u2010fidelity drug transport, dissolution, and absorption model in the human stomach and GIT using the recently published Quasi\u20103D framework. The computational results showed that MAT was able to match the experimental concentration results better than the traditional compartmental models. In this study, we adapted MAT, to predict the pharmacokinetics of orally delivered HCQ in healthy subjects. The computational results matched the experimental concentration results. The simulated stomach and intestinal fluid and enterocyte concentrations were compared with the in vitro CC50 values. While the peak enterocyte concentrations were several orders lower than the in vitro CC50 values, the peak stomach and the intestinal fluid concentrations were only one order smaller than the in vitro CC50 values. In particular, the peak stomach and the duodenum fluid concentrations were just 3\u00d7 smaller than the in vitro CC50 values. This implies that the lumen walls are much more susceptible to cytotoxicity\u2010based damage than the enterocyte layers. We envision that MAT can be used to optimize the dosing regimen of HCQ by maximizing its bioavailability, while simultaneously minimizing the cytotoxic damage.<\/jats:p>","DOI":"10.1002\/cnm.3403","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T07:06:19Z","timestamp":1602140779000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A multiscale absorption and transit model for oral delivery of hydroxychloroquine: Pharmacokinetic modeling and intestinal concentration prediction to assess toxicity and drug\u2010induced damage in healthy subjects"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8046-673X","authenticated-orcid":false,"given":"Ravishekar","family":"Kannan","sequence":"first","affiliation":[{"name":"CFD Research Corporation  Huntsville Alabama 35806 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"Przekwas","sequence":"additional","affiliation":[{"name":"CFD Research Corporation  Huntsville Alabama 35806 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/cases-updates\/cases-in-us.html. 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