{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:31:39Z","timestamp":1788298299335,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The efficacy of the combination therapy of albendazole and ivermectin against <jats:italic>Trichuris trichiura<\/jats:italic> infection is higher in Tanzania than in C\u00f4te d'Ivoire. This study therefore aimed to investigate the difference between the population pharmacokinetics (PK) at these study sites and to determine if an exposure\u2010response analysis could explain the low efficacy of the combination therapy in C\u00f4te d'Ivoire. Twenty\u2010four participants (aged 12\u201019 years) receiving single doses of ivermectin (200 \u00b5g\/kg) and albendazole (400 mg) were included in the population PK modeling. A regression analysis was performed to investigate the relationship between the reduction of fecal whipworm eggs and different exposure metrics (peak concentration, area under the plasma drug concentration\u2010time curve [AUC], and time above a certain threshold). The PK profile of ivermectin was best described by a one\u2010compartment model, first\u2010order absorption, and no delay in absorption, with the absorption rate constant estimated as 0.26 per h, an apparent volume of distribution of 162.43 L, and an apparent clearance of 7.82 L\/h. In Tanzania, all patients showed a very high reduction in egg count independent of exposure. In C\u00f4te d'Ivoire, a relationship was found between higher ivermectin exposure and egg reduction, although not statistically significant. There was no significant difference between the PK profiles at both study sites, despite a difference in clinical outcome. Model\u2010based simulations indicate that higher ivermectin doses such as 400 and 600 \u00b5g\/kg may be associated with reduced egg count. Larger clinical studies are warranted to explore further the exposure\u2010efficacy response relationship at 200 \u00b5g\/kg and higher ivermectin doses in adults and children.<\/jats:p>","DOI":"10.1002\/jcph.6158","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T05:29:48Z","timestamp":1730957388000},"page":"433-440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacometric Analysis to Describe Pharmacokinetics and Exposure\u2010Efficacy Response of Ivermectin in Adolescents Infected with <i>Trichuris trichiura<\/i>"],"prefix":"10.1002","volume":"65","author":[{"given":"David T.","family":"Ajayi","sequence":"first","affiliation":[{"name":"Pharmacometrics Africa NPC Groote Schuur Hospital  Cape Town South Africa"},{"name":"Department of Public Health Chrisland University  Abeokuta 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University Hospital Basel  Basel Switzerland"},{"name":"Swiss Tropical and Public Health Institute  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Buettcher","sequence":"additional","affiliation":[{"name":"Paediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel (UKBB), University of Basel  Basel Switzerland"},{"name":"Paediatric Infectious Diseases Department of Paediatrics Children's Hospital of Central Switzerland (KidZ) Lucerne Cantonal Hospital  Lucerne Switzerland"},{"name":"Faculty of Health Science and Medicine University Lucerne  Lucerne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean T.","family":"Coulibaly","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Formation et de Recherche Biosciences Universit\u00e9 F\u00e9lix Houphou\u00ebt\u2010Boigny  Abidjan C\u00f4te d'Ivoire"},{"name":"Centre Suisse de Recherches Scientifiques en C\u00f4te d'Ivoire 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