{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:52:36Z","timestamp":1791514356015,"version":"4.3.4"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000781","name":"The European Research Council","doi-asserted-by":"crossref","award":["CoG 614739"],"award-info":[{"award-number":["CoG 614739"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Eckenstein-Geigy Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Albendazole is the most commonly used drug in preventive chemotherapy programmes against soil-transmitted helminth (STH) infections, with the standard dose of 400 mg resulting in suboptimal clinical outcomes. Population pharmacokinetic (PK) models that could inform dosing strategies are not yet available.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A population pharmacokinetic model was developed based on micro-blood samples collected from 252 patients aged 2 to 65 years, infected with either hookworm or Trichuris trichiura and treated with albendazole doses ranging from of 200 to 800 mg. An exposure\u2013response analysis was performed relating albendazole and its two metabolites to cure rates and egg reduction rates (ERR). Finally, model-based simulations were conducted to determine equivalent exposure coverage in infants to adults.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A population PK model, with one distribution compartment for each compound and one peripheral compartment, following oral administration with a lag time, assuming first-order absorption and linear elimination, best described the concentration\u2013time profiles. Clearance and volume parameters were scaled to body size (weight for albendazole and height for albendazole sulfoxide and sulfone). Dose proportionality was observed for the active metabolite, albendazole sulfoxide, but only in hookworm-infected individuals, with increasing exposure resulting in increased ERR. Exposure of sulfoxide was lowest in the tallest individuals.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Pharmacometric simulations indicate that doses up to 800 mg could further increase albendazole efficacy in hookworm-infected adults, whereas the standard dose of 400 mg is sufficient in the youngest age cohorts. In the absence of evidence-based arguments for adjusting albendazole doses in T. trichiura-infected individuals, the search for new treatment options is further emphasized.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac020","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T20:11:36Z","timestamp":1643055096000},"page":"1082-1093","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacokinetic modelling and simulation to optimize albendazole dosing in hookworm- or <i>Trichuris trichiura-<\/i>infected infants to adults"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7073-0744","authenticated-orcid":false,"given":"Daniela","family":"Hofmann","sequence":"first","affiliation":[{"name":"Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0813-4463","authenticated-orcid":false,"given":"Janneke M.","family":"Brussee","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"},{"name":"Pediatric Pharmacology and Pharmacometrics, University Children\u2019s Hospital Basel, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica D.","family":"Schulz","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean T.","family":"Coulibaly","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"},{"name":"Unit\u00e9 de Formation et de Recherche Biosciences, Universit\u00e9 F\u00e9lix Houphou\u00ebt\u2013Boigny, Abidjan, C\u00f4te d\u2019Ivoire"},{"name":"Centre Suisse de Recherches Scientifiques en C\u00f4te d\u2019Ivoire, Abidjan, C\u00f4te d\u2019Ivoire"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2597-1228","authenticated-orcid":false,"given":"Marc","family":"Pfister","sequence":"additional","affiliation":[{"name":"Pediatric Pharmacology and Pharmacometrics, University Children\u2019s Hospital Basel, University of Basel, Basel, Switzerland"},{"name":"Certara LP, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0290-3521","authenticated-orcid":false,"given":"Jennifer","family":"Keiser","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"key":"2022033111270290400_dkac020-B1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/jac\/41.2.145","article-title":"Albendazole","volume":"41","author":"Venkatesan","year":"1998","journal-title":"J Antimicrob Chemother"},{"key":"2022033111270290400_dkac020-B2","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s40262-016-0467-3","article-title":"Lack of clinical pharmacokinetic studies to optimize the treatment of neglected tropical diseases: A systematic review","volume":"56","author":"Verrest","year":"2017","journal-title":"Clin Pharmacokinet"},{"key":"2022033111270290400_dkac020-B3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0001-706X(03)00031-7","article-title":"Albendazole, mebendazole and praziquantel. 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