{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:31:43Z","timestamp":1788298303884,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:00:00Z","timestamp":1727049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p><jats:italic>Trichuris trichiura<\/jats:italic> is a soil\u2010transmitted helminth causing intestinal disease. Albendazole is the standard treatment despite its moderate efficacy, which is improved when co\u2010administered with ivermectin. A fixed\u2010dose combination adds practical advantages mainly for mass drug administration. The aim of this article is to define the population pharmacokinetic models and exposure\u2013response of an innovative albendazole\/ivermectin combination. Data were obtained from a phase I clinical trial in healthy adults and from a phase II trial in children and adolescents infected with <jats:italic>T.\u2009trichiura<\/jats:italic>. Nonlinear mixed\u2010effects models were built for albendazole and ivermectin using NONMEM\u00ae. Area under the curve was calculated using the empirical Bayes estimates of the pharmacokinetic parameters of each individual and used for evaluation of exposure\u2013response between cure rate and pharmacokinetic exposure. The pharmacokinetics of albendazole was described using a two\u2010compartmental model with first\u2010order absorption and the pharmacokinetics of ivermectin was described using a two\u2010compartmental model with zero\u2010order followed by first\u2010order absorption. Clearance and volume of distribution increased with body weight for both albendazole and ivermectin. Day 1 area under the curve of albendazole and ivermectin from the children and adolescents treated with the combination regimens were similar to the healthy adults treated with control drugs. A flat exposure\u2013response relationship was observed between the cure rate and drug exposure. Population pharmacokinetic of a combination of albendazole and ivermectin in children, adolescents, and adults, either healthy or infected by <jats:italic>T.\u2009trichiura<\/jats:italic> was described. The dosage selected in the phase II trial was appropriate for the subsequent phase III.<\/jats:p>","DOI":"10.1002\/cpt.3424","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T08:38:08Z","timestamp":1727080688000},"page":"203-213","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Population Pharmacokinetics and Exposure\u2013Response Analysis of a Fixed\u2010Dose Combination of Ivermectin and Albendazole in Children, Adolescents, and Adults"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7042-5675","authenticated-orcid":false,"given":"Jaime","family":"Algorta","sequence":"first","affiliation":[{"name":"Clinical Research Department, Liconsa  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Kepha","sequence":"additional","affiliation":[{"name":"Eastern and Southern Africa Centre of International Parasite Control Kenya Medical Research Institute (KEMRI)  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9054-1211","authenticated-orcid":false,"given":"Alejandro","family":"Krolewiecki","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones de Enfermedades Tropicales, Universidad Nacional de Salta  Oran Salta Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbin","family":"Li","sequence":"additional","affiliation":[{"name":"QuanTx Consulting  Mountain View California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Giang","sequence":"additional","affiliation":[{"name":"QuanTx Consulting  Mountain View California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Fleitas","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic\u2010Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Mwandawiro","sequence":"additional","affiliation":[{"name":"Eastern and Southern Africa Centre of International Parasite Control Kenya Medical Research Institute (KEMRI)  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic\u2010Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the STOP Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"key":"e_1_2_11_1_1","first-page":"1","article-title":"Soil\u2010transmitted helminth infections","volume":"6736","author":"Jourdan P.M.","year":"2017","journal-title":"Lancet"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32279-7"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2011.08.013"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j4307"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003897"},{"key":"e_1_2_11_6_1","first-page":"e64","article-title":"A call to strengthen the global strategy against schistosomiasis and soil\u2010transmitted helminthiasis: the time is now","volume":"3099","author":"Lo N.C.","year":"2016","journal-title":"Lancet Infect. 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