{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T07:30:45Z","timestamp":1776843045809,"version":"3.51.2"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["220211"],"award-info":[{"award-number":["220211"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Global efforts to eliminate onchocerciasis are hampered by the lack of a macrofilaricidal drug capable of killing adult parasites. Oxfendazole, a veterinary anthelminthic, exhibits macrofilaricidal activity and holds promise to shorten treatment durations. Phase 1 studies in healthy Caucasian adults demonstrated favorable pharmacokinetics and safety using a veterinary oral liquid formulation. More recently, a Phase 1 bioavailability trial (NCT04920292) evaluated a field\u2010applicable tablet formulation in healthy African adults. This study presents a secondary analysis to (i) characterize the population pharmacokinetics of oxfendazole and its major metabolites in healthy African adults receiving the tablet formulation and (ii) propose a dosing regimen for Phase 2 evaluation in patients with onchocerciasis. Thirty healthy African adults were enrolled, and plasma concentration\u2013time profiles of oxfendazole, fenbendazole, and oxfendazole sulfone were obtained from 24 participants who received oxfendazole (8 per dose group: 100\u2009mg single dose, 400\u2009mg single dose, 400\u2009mg once daily for 5\u2009days). All cohorts were pooled and analyzed using nonlinear mixed effects modeling. Oxfendazole absorption was best described by first\u2010order kinetics with first\u2010pass metabolism. Dose\u2010limited bioavailability was evident. Disposition was best described by one\u2010compartment models with linear elimination. Simulations suggested that 400\u2009mg once daily (or 50\u2009mg twice daily) for 5\u2009days is required to achieve putative exposure targets (&gt;\u2009200\u2009ng\/mL for 5\u2009days), with low risk of safety concerns. The population pharmacokinetic model adequately described oxfendazole pharmacokinetics in healthy African adults and supports dosing selection for future clinical trials.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    Identifier: NCT04920292\n                  <\/jats:p>","DOI":"10.1002\/psp4.70189","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T17:40:17Z","timestamp":1770658817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repurposing Oxfendazole for Onchocerciasis: Population Pharmacokinetics of a Tablet Formulation in Healthy African Adults"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1146-3452","authenticated-orcid":false,"given":"Frauke","family":"Assmus","sequence":"first","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine Mahidol University  Bangkok Thailand"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayorinde","family":"Adehin","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine Mahidol University  Bangkok Thailand"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard M.","family":"Hoglund","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine Mahidol University  Bangkok Thailand"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9587-0540","authenticated-orcid":false,"given":"Gloria","family":"Nyaulingo","sequence":"additional","affiliation":[{"name":"Ifakara Health Institute  Bagamoyo Tanzania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hussein","family":"Mbarak","sequence":"additional","affiliation":[{"name":"Ifakara Health Institute  Bagamoyo Tanzania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Said","family":"Jongo","sequence":"additional","affiliation":[{"name":"Ifakara Health Institute  Bagamoyo Tanzania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eveline","family":"Ackermann","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute  Allschwil Switzerland"},{"name":"University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5322-3473","authenticated-orcid":false,"given":"Elisabeth","family":"Reus","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute  Allschwil Switzerland"},{"name":"University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Keiser","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute  Allschwil Switzerland"},{"name":"University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0216-7341","authenticated-orcid":false,"given":"Fabiana Barreira Da Silva","family":"Rocha","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative  Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Specht","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative  Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Scandale","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative  Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4566-4030","authenticated-orcid":false,"given":"Joel","family":"Tarning","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine Mahidol University  Bangkok Thailand"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine University of Oxford  Oxford UK"},{"name":"Infectious Diseases Data Observatory University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Centers for Disease Control and Prevention \u201cOnchocerciasis FAQs \u201d(2020) https:\/\/www.cdc.gov\/parasites\/onchocerciasis\/gen_info\/faqs.html."},{"key":"e_1_2_10_3_1","unstructured":"World Health Organisation \u201cOnchocerciasis Key Facts \u201d(2022) https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/onchocerciasis."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-016-1993-7"},{"key":"e_1_2_10_5_1","unstructured":"S. R.Jada J. Y.Carter J.Rovarini et\u00a0al. \u201cTackling Onchocerciasisassociated Epilepsy New Evidence and Recommendations for Policymakers \u201d(2023)."},{"key":"e_1_2_10_6_1","volume-title":"Ending the Neglect to Attain the Sustainable Development Goals: A Road Map for Neglected Tropical Diseases 2021\u20132030: Overview","author":"World Health Organization","year":"2020"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2022.10.006"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.9b00469"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000217"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2883-2-S1-S4"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)11094-1"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.12688\/gatesopenres.13067.1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix1137"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000998"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2018.1555241"},{"key":"e_1_2_10_16_1","unstructured":"EMEA \u201cEuropean Medicines Agency Veterinary Medicines and Inspections Oxfendazole (Extrapolation to All Ruminants) Summary Report 4. EMEA\/MRL\/888\/03\u2010FINAL \u201d(2004)."},{"key":"e_1_2_10_17_1","unstructured":"FDA \u201cFood and Drug Administration FDA Center for Veterinary Medicine FDA Approved Animal Drug Products the Green Book \u201daccessed June 5 2023 https:\/\/animaldrugsatfda.fda.gov\/adafda\/views\/#\/search."},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-4758(90)90227-U"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0020-7519(88)90175-0"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00245a029"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-4758(90)90231-R"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008427"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007556"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581815569582"},{"key":"e_1_2_10_25_1","unstructured":"\u201cOxfendazole Development Group (ODG) \u201daccessed July 6 2023 https:\/\/oxfendazoledevelopmentgroup.org\/."},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02255-18"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01018-20"},{"key":"e_1_2_10_28_1","unstructured":"H.Mbaraka E.Ackermann G.Nyaulingo et\u00a0al. \u201cPharmacokinetics Safety and Tolerability of an Oxfendazole Tablet Formulation: A Phase 1 Randomized Placebo\u2010Controlled Trial in Healthy African Volunteers \u201d(2025) (accepted AAC)."},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02129-20"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01113502"},{"key":"e_1_2_10_31_1","unstructured":"Drugs for Neglected Diseases Initiative \u201cDNDi's Drug Development Project Portfolio: Three Projects for Onchocerciasis \u201daccessed November 13 2023."},{"key":"e_1_2_10_32_1","unstructured":"World Health Organization \u201cWHO\/MG\/15.20. Report of the Consultative Meetings on Strategic Options and Alternative Treatment Strategies for Accelerating Onchocerciasis Elimination in Africa \u201d(2015) African Programme for Onchocerciasis Control (APOC)."},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01432-21"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.003319"},{"key":"e_1_2_10_35_1","unstructured":"D.FisherandS.Shafer \u201cFisher\/Shafer NONMEM Workshop Pharmacokinetic and Pharmacodynamic Analysis With NONMEM \u201dBasic Concepts Het Pand Ghent Belgium T2007."},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1991.44.151"},{"key":"e_1_2_10_37_1","article-title":"Current Perspective of New Anti\u2010Wolbachial and Direct\u2010Acting Macrofilaricidal Drugs as Treatment Strategies for Human Filariasis","volume":"10","author":"Ehrens A.","year":"2022","journal-title":"GMS Infectious Diseases"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007026"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fitd.2022.982421"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw150"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70189","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.70189","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70189","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:18:20Z","timestamp":1773029900000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/psp4.70189"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70189","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-09-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70189"}}