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Asynchronized ring-stage 3D7 parasites were maintained in the extracapillary space under continuous-flow culture conditions that supported sustained growth across two consecutive 48 h intraerythrocytic life cycles. The observed parasitemia dynamics were comparable in static and dynamic drug-free controls. Target total plasma concentration time profiles for intravenous mefloquine were generated using a pharmacokinetic (PK) simulation study based on previously reported compartmental models from adult malaria patients and subsequently implemented in the HFIM through programmed dilution to mimic first-order elimination, with dosing simulated as a 100 mg intravenous (IV) bolus every 24 h for 3 days. The HFIM exposure profile maintained clinically relevant peak concentrations with the long clinical PK half-life of mefloquine. Under these dynamic exposure conditions, mefloquine produced sustained suppression of parasitemia across successive life cycles relative to both control conditions, consistent with concentration-driven blood-stage activity. The estimated IC50 was 0.03 mg\/L. Together, this study demonstrated that the commonly used plastic-based HFIM can simulate clinically relevant PK profiles and characterize the antimalarial PD against blood-stage P. falciparum. This addresses limitations of static in vitro assays and reduces the reliance on animal models, where preclinical-to-clinical concordance can be poor. Thereby, HFIM provides a promising framework for optimizing antimalarial dosing strategies. Future studies will extend this approach to rational evaluation of combination therapies using PK\/PD-guided regimen design to improve clinical relevance.<\/jats:p>","DOI":"10.1021\/acsptsci.6c00482","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:02:11Z","timestamp":1790704931000},"page":"2983-2990","source":"Crossref","is-referenced-by-count":0,"title":["Translational Pharmacokinetic\nand Pharmacodynamic\nEvaluation of Mefloquine Against\n                    <i>Plasmodium falciparum<\/i>\n                    Using a Hollow Fiber Infection Model"],"prefix":"10.1021","volume":"9","author":[{"given":"Sabiha R.","family":"Mim","sequence":"first","affiliation":[{"name":"University of Florida , , ,","place":["Orlando, Florida, United States, 32827"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiana","family":"Pica","sequence":"additional","affiliation":[{"name":"University of Florida , , ,","place":["Orlando, Florida, United States, 32827"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Liu","sequence":"additional","affiliation":[{"name":"St. Jude Children\u2019s Research Hospital , , ,","place":["Memphis, Tennessee, United States, 38105"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zang","sequence":"additional","affiliation":[{"name":"University of Florida, College of Pharmacy , , Center Drive , ,","place":["Gainesville, Florida, United States, 32610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinzhi","family":"Lang","sequence":"additional","affiliation":[{"name":"St. Jude Children\u2019s Research Hospital , , ,","place":["Memphis, Tennessee, United States, 38105"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7352-3097","authenticated-orcid":true,"given":"Ju\u0308rgen B.","family":"Bulitta","sequence":"additional","affiliation":[{"name":"St. Jude Children\u2019s Research Hospital , , ,","place":["Memphis, Tennessee, United States, 38105"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3625-0186","authenticated-orcid":true,"given":"Francine Johansson","family":"Azeredo","sequence":"additional","affiliation":[{"name":"University of Florida , , ,","place":["Orlando, Florida, United States, 32827"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"2026100909110167400_cit1","unstructured":"World malaria report\n          2024. https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2024 (accessed 2026-01-28)."},{"key":"2026100909110167400_cit2","unstructured":"Fact sheet about\nmalaria. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/malaria (accessed 2026\u201301\u201328)."},{"issue":"1","key":"2026100909110167400_cit3","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s12936-022-04115-8","article-title":"Malaria\nChemoprevention and Drug Resistance: A Review of the Literature and\nPolicy Implications","volume":"21","author":"Plowe","year":"2022","journal-title":"Malar. 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Pharmacol."},{"issue":"1","key":"2026100909110167400_cit7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1002\/9780470559277.ch150194","article-title":"Hollow-Fiber Methodology\nfor Pharmacokinetic\/Pharmacodynamic Studies of Antimalarial Compounds","volume":"8","author":"Caton","year":"2016","journal-title":"Curr. Protoc. Chem. Biol."},{"issue":"3","key":"2026100909110167400_cit8","doi-asserted-by":"publisher","first-page":"106616","DOI":"10.1016\/j.ijantimicag.2022.106616","article-title":"Pharmacokinetic\/Pharmacodynamic Models\nfor Time Courses of Antibiotic Effects","volume":"60","author":"Minichmayr","year":"2022","journal-title":"Int.\nJ. Antimicrob. 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J."}],"container-title":["ACS Pharmacology &amp; Translational\nScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsptsci.6c00482","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aptsfn\/article-pdf\/9\/10\/2983\/68701868\/acsptsci.6c00482.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aptsfn\/article-pdf\/9\/10\/2983\/68701868\/acsptsci.6c00482.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:31:25Z","timestamp":1791552685000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aptsfn\/article\/9\/10\/2983\/5441778\/Translational-Pharmacokinetic-and-Pharmacodynamic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":49,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,9,29]]},"published-print":{"date-parts":[[2026,10,9]]}},"URL":"https:\/\/doi.org\/10.1021\/acsptsci.6c00482","relation":{},"ISSN":["2575-9108"],"issn-type":[{"value":"2575-9108","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]}}}