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The study aimed to predict the potential dose regimens of quinine when coadministered with phenobarbital in adult patients with cerebral malaria and complications (e.g., lactic acidosis and acute renal failure) and concurrent with seizures and acute renal failure who carry wild\u2010type and polymorphic <jats:italic>CYP2C19<\/jats:italic>. The whole\u2010body physiologically based pharmacokinetic (PBPK) models for quinine, phenobarbital, and quinine\u2013phenobarbital coadministration were constructed based on the previously published information using Simbiology\u00ae. Four published articles were used for model validation. A total of 100 virtual patients were simulated based on the 14\u2010day and 3\u2010day courses of treatment. using the drug\u2013drug interaction approach. The predicted results were within 15% of the observed values. Standard phenobarbital dose, when administered with quinine, is suitable for all groups with single or continuous seizures regardless of <jats:italic>CYP2C19<\/jats:italic>\u00a0genotype, renal failure, and lactic acidosis. Dose adjustment based on area under the curve ratio provided inappropriate quinine concentrations. The recommended dose of quinine when coadministered with phenobarbital based on the PBPK model for all groups is a loading dose of 2000\u00a0mg intravenous (i.v.) infusion rate 250\u00a0mg\/h followed by 1200\u00a0mg i.v. rate 150\u00a0mg\/h. The developed PBPK models are credible for further simulations. Because the predicted quinine doses in all groups were similar regardless of the <jats:italic>CYP2C19<\/jats:italic>\u00a0genotype, genotyping may not be required.<\/jats:p>","DOI":"10.1002\/psp4.12737","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T09:19:25Z","timestamp":1635931165000},"page":"104-115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Physiologically based pharmacokinetic modeling for dose optimization of quinine\u2013phenobarbital coadministration in patients with cerebral malaria"],"prefix":"10.1002","volume":"11","author":[{"given":"Teerachat","family":"Sae\u2010heng","sequence":"first","affiliation":[{"name":"Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma Chulabhorn International College Thammasat University (Rangsit Campus)  Pathumthani Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajith Kumar Reddy","family":"Rajoli","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Siccardi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juntra","family":"Karbwang","sequence":"additional","affiliation":[{"name":"Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma Chulabhorn International College Thammasat University (Rangsit Campus)  Pathumthani Thailand"},{"name":"Drug Discovery and Development Center Office of Advanced Science and Technology Thammasat University (Rangsit Campus)  Pathumthani Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kesara","family":"Na\u2010Bangchang","sequence":"additional","affiliation":[{"name":"Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma Chulabhorn International College Thammasat University (Rangsit Campus)  Pathumthani Thailand"},{"name":"Drug Discovery and Development Center Office of Advanced Science and Technology Thammasat University (Rangsit Campus)  Pathumthani Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"issue":"8","key":"e_1_2_8_2_1","first-page":"213","article-title":"Epidemiology of cerebral malaria and its mortality","volume":"47","author":"Durrani AB","year":"1997","journal-title":"J Pak Med Assoc"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(05)70247-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.69.4.433"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-019-2670-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2005.52704.x"},{"issue":"2","key":"e_1_2_8_7_1","first-page":"CD002152","article-title":"Routine anticonvulsants for treating cerebral malaria","volume":"2","author":"Meremikwu M","year":"2000","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.12058"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050703"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2710.2006.00712.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-003-0637-8"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fpc.0000182784.77630.48"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.066845"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03671.x"},{"issue":"8","key":"e_1_2_8_15_1","first-page":"155","article-title":"Species differences in phenobarbital\u2010mediated UGT gene induction in rat and human liver microtissues","volume":"29","author":"Plummer S","year":"2020","journal-title":"Toxicol Rep"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.2515\/therapie\/2011071"},{"issue":"1","key":"e_1_2_8_17_1","first-page":"1","article-title":"Clinical features and mortality associated with severe malaria in adults in southern Mauritania","volume":"6","author":"Boushab BM","year":"2021","journal-title":"Trop Med Infect Dis"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1013"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1721"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-014-0227-1"},{"key":"e_1_2_8_21_1","unstructured":"US Food and Drug Administration.Qualaquin [product label].https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2010\/021799s011lbl.pdf.Published 2013. 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