{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:48:09Z","timestamp":1791503289917,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["2R56DE02169707A1, and 1R01DE02788401A1"],"award-info":[{"award-number":["2R56DE02169707A1, and 1R01DE02788401A1"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical &amp; Exp Dental Res"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Sj\u00f6gren's syndrome (SS) is an autoimmune disease that causes chronic inflammation of the salivary glands leading to secretory dysfunction. Previous studies demonstrated that aspirin\u2010triggered resolvin D1 (AT\u2010RvD1) reduces inflammation and restores tissue integrity in salivary glands. Specifically, progression of SS\u2010like features in NOD\/ShiLtJ mice can be systemically halted using AT\u2010RvD1 prior or after disease onset to downregulate proinflammatory cytokines, upregulate anti\u2010inflammatory molecules, and restore saliva production. Therefore, the goal of this paper was to create a physiologically based pharmacokinetic (PBPK) model to offer a reasonable starting point for required total AT\u2010RvD1 dosage to be administered in future mice and humans thereby eliminating the need for excessive use of animals and humans in preclinical and clinical trials, respectively. Likewise, PBPK modeling was employed to increase the range of testable scenarios for elucidating the mechanisms under consideration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Pharmacokinetics following intravenous administration of a 0.1 mg\/kg dose of AT\u2010RvD1 in NOD\/ShiLtJ were predicted in both plasma and saliva using PBPK modeling with PK\u2010Sim\u00ae and MoBi\u00ae Version 7.4 software.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The model provides high\u2010value pathways for future validation via in vivo studies in NOD\/ShiLtJ to corroborate the findings themselves while also establishing this method as a means to better target drug development and clinical study design.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Clinical and basic research would benefit from knowledge of the potential offered by computer modeling. Specifically, short\u2010term utility of these pharmacokinetic modeling findings involves improved targeting of in vivo studies as well as longer term prospects for drug development and\/or better designs for clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cre2.260","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T17:53:30Z","timestamp":1576778010000},"page":"225-235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Predictive modeling of aspirin\u2010triggered resolvin D1 pharmacokinetics for the study of Sj\u00f6gren's syndrome"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3819-9054","authenticated-orcid":false,"given":"Venkata Kashyap","family":"Yellepeddi","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pediatrics, School of Medicine University of Utah  Salt Lake City Utah"},{"name":"Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy University of Utah  Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0628-8645","authenticated-orcid":false,"given":"Olga J.","family":"Baker","sequence":"additional","affiliation":[{"name":"School of Dentistry University of Utah  Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2016.1162348"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00144.2008"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2017.11.031"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201216"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2017.03.005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj070355"},{"key":"e_1_2_7_8_1","unstructured":"Community O. 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