{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:26:59Z","timestamp":1790000819367,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010005","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000}}],"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004423","name":"World Health Organization","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004423","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"\nBackground<\/jats:title>\nOnchocerciasis (\u201criver blindness\u201d), is a neglected tropical disease caused by the filarial nematode Onchocerca volvulus<\/jats:italic> and transmitted to humans through repeated bites by infective blackflies of the genus Simulium<\/jats:italic>. Moxidectin was approved by the United States Food and Drug Administration in 2018 for the treatment of onchocerciasis in people at least 12 years of age. The pharmacokinetics of orally administered moxidectin in 18- to 60-year-old men and women infected with Onchocerca volvulus<\/jats:italic> were investigated in a single-center, ivermectin-controlled, double-blind, randomized, single-ascending-dose, ascending severity of infection study in Ghana.<\/jats:p>\n<\/jats:sec>\n\nMethodology\/Principal findings<\/jats:title>\nParticipants were randomized to either a single dose of 2, 4 or 8 mg moxidectin or ivermectin. Pharmacokinetic samples were collected prior to dosing and at intervals up to 12 months post-dose from 33 and 34 individuals treated with 2 and 4 mg moxidectin, respectively and up to 18 months post-dose from 31 individuals treated with 8 mg moxidectin. Moxidectin plasma concentrations were determined using high-performance liquid chromatography with fluorescence detection. Moxidectin plasma AUC0-\u221e<\/jats:sub> (2 mg: 26.7\u201331.7 days*ng\/mL, 4 mg: 39.1\u201360.0 days*ng\/mL, 8 mg: 99.5\u2013129.0 days*ng\/mL) and Cmax<\/jats:sub> (2mg, 16.2 to17.3 ng\/mL, 4 mg: 33.4 to 35.0 ng\/mL, 8 mg: 55.7 to 74.4 ng\/mL) were dose-proportional and independent of severity of infection. Maximum plasma concentrations were achieved 4 hours after drug administration. The mean terminal half-lives of moxidectin were 20.6, 17.7, and 23.3 days at the 2, 4 and 8 mg dose levels, respectively.<\/jats:p>\n<\/jats:sec>\n\nConclusion\/Significance<\/jats:title>\nWe found no relationship between severity of infection (mild, moderate or severe) and exposure parameters (AUC0-\u221e<\/jats:sub> and Cmax<\/jats:sub>), T1\/2<\/jats:sub> and Tmax<\/jats:sub> for moxidectin. Tmax<\/jats:sub>, volume of distribution (V\/F) and oral clearance (CL\/F) are similar to those in healthy volunteers from Europe. From a pharmacokinetic perspective, moxidectin is an attractive long-acting therapeutic option for the treatment of human onchocerciasis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0010005","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T17:46:30Z","timestamp":1648230390000},"page":"e0010005","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Pharmacokinetics of oral moxidectin in individuals with Onchocerca volvulus infection"],"prefix":"10.1371","volume":"16","author":[{"given":"Beesan","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Opoku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon K.","family":"Attah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwablah","family":"Awadzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette C.","family":"Kuesel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis","family":"Lazdins-Helds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Rayner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Ryg-Cornejo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Fleckenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"pntd.0010005.ref001","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/B978-0-12-803678-5.00206-X","volume-title":"International Encyclopedia of Public Health","author":"JHF Remme","year":"2017","edition":"2"},{"issue":"5","key":"pntd.0010005.ref002","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003542","article-title":"Managing the fight against onchocerciasis in Africa: APOC experience.","volume":"9","author":"G Fobi","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0010005.ref003","unstructured":"World Health Organization (WHO). Onchocerciasis Fact Sheet [Internet]. Geneva; 2019 [cited 2021 Oct 29]. 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