{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:31:42Z","timestamp":1788298302288,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T00:00:00Z","timestamp":1694390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ivermectin (IVM) is a drug of choice used with albendazole for mass drug administration (MDA) to halt transmission of lymphatic filariasis. We investigated IVM pharmacokinetic (PK) variability for its dose optimization during MDA. PK samples were collected at 0, 2, 4, and 6\u2009h from individuals weighing greater than 15 kg (<jats:italic>n<\/jats:italic>\u2009=\u2009468) receiving IVM (3\u2010, 6\u2010, 9\u2010, or 12\u2009mg) and ALB (400\u2009mg) during an MDA campaign in Tanzania. Individual characteristics, including demographics, laboratory\/clinical parameters, and pharmacogenetic variations were assessed. IVM plasma concentrations were quantified by liquid\u2010chromatography tandem mass spectrometry and analyzed using population\u2010(PopPK) modeling. A two\u2010compartment model with transit absorption kinetics, and allometrically scaled oral clearance (CL\/F) and central volume (<jats:italic>V<\/jats:italic><jats:sub>c<\/jats:sub>\/F) was adapted. Fitting of the model to the data identified 48% higher bioavailability for the 3\u2009mg dose compared to higher doses and identified a subpopulation with 97% higher mean transit time (MTT). The final estimates for CL\/F, <jats:italic>V<\/jats:italic><jats:sub>c<\/jats:sub>\/F, intercompartment clearance, peripheral volume, MTT, and absorption rate constant for a 70 kg person (on dose other than 3\u2009mg) were 7.7\u2009L\/h, 147\u2009L, 20.4\u2009L\/h, 207\u2009L, 1.5\u2009h, and 0.71\/h, respectively. Monte\u2010Carlo simulations indicated that weight\u2010based dosing provides comparable exposure across weight bands, but height\u2010based dosing with capping IVM dose at 12\u2009mg for individuals with height greater than 160\u2009cm underdoses those weighing greater than 70 kg. Variability in IVM PKs is partly explained by body weight and dose. The established PopPK model can be used for IVM dose optimization. Height\u2010based pole dosing results in varying IVM exposure in different weight bands, hence using weighing scales for IVM dosing during MDA is recommended.<\/jats:p>","DOI":"10.1002\/psp4.13038","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T10:21:36Z","timestamp":1693218096000},"page":"1884-1896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of Tanzania"],"prefix":"10.1002","volume":"12","author":[{"given":"Adam M.","family":"Fimbo","sequence":"first","affiliation":[{"name":"Department of Global Public Health Karolinska Institutet, Karolinska University Hospital  Stockholm Sweden"},{"name":"Tanzania Medicines and Medical Devices Authority (TMDA)  Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eulambius M.","family":"Mlugu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmacy Practice, School of Pharmacy Muhimbili University of Health and Allied Sciences  Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliford Ngaimisi","family":"Kitabi","sequence":"additional","affiliation":[{"name":"Division of Pharmacometrics Office of Clinical Pharmacology, US Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald S.","family":"Kulwa","sequence":"additional","affiliation":[{"name":"Tanzania Medicines and Medical Devices Authority (TMDA)  Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A.","family":"Iwodyah","sequence":"additional","affiliation":[{"name":"Tanzania Medicines and Medical Devices Authority (TMDA)  Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajabu Hussein","family":"Mnkugwe","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Biomedical Sciences, Campus College of Medicine Muhimbili University of Health and Allied Sciences  Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter P.","family":"Kunambi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Biomedical Sciences, Campus College of Medicine Muhimbili University of Health and Allied Sciences  Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alpha","family":"Malishee","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, Tanga Center  Tanga Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Appolinary A. R.","family":"Kamuhabwa","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, School of Pharmacy Muhimbili University of Health and Allied Sciences  Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omary M.","family":"Minzi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, School of Pharmacy Muhimbili University of Health and Allied Sciences  Dar es Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9788-0790","authenticated-orcid":false,"given":"Eleni","family":"Aklillu","sequence":"additional","affiliation":[{"name":"Department of Global Public Health Karolinska Institutet, Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40249-018-0420-9"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/tropicalmed2030032"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0231541"},{"key":"e_1_2_10_5_1","unstructured":"World Health Organization.Lymphatic filariasis.2022[cited 2023 April 11].https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/lymphatic\u2010filariasis"},{"key":"e_1_2_10_6_1","volume-title":"Guideline: Alternative Mass Drug Administration Regimens to Eliminate Lymphatic Filariasis","author":"World Health Organization","year":"2017"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph13080196"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2020.10.005"},{"key":"e_1_2_10_9_1","unstructured":"Medicine.com.Albendazole.2020. [cited 2023 April 11].https:\/\/www.medicine.com\/drug\/albendazole\/hcp"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2013.12.021"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2012.04.009"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15050594"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-021-03025-z"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/004982598239597"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2007.76.1153"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006020"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-017-1923-8"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2017.10.006"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00843-13"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2005.05.017"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0243-9"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/009127002237994"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-007-9000-9"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.09.035"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2007.07.011"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13840"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz083"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9051550"},{"key":"e_1_2_10_29_1","unstructured":"WHO.Preventive chemotherapy in human helminthiasis \u2013 coordinated use of anthelminthic drugs in control interventions.2006[cited 15 April 2023].https:\/\/www.who.int\/publications\/i\/item\/9241547103"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2019.04.007"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-020-09695-z"},{"key":"e_1_2_10_32_1","volume-title":"Preventive Chemotherapy in Human Helminthiasis: Coordinated Use of Anthelminthic Drugs in Control Interventions: a Manual for Health Professionals and Programme Managers","author":"Crompton DWT","year":"2006"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007541"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14694"},{"key":"e_1_2_10_35_1","first-page":"438","article-title":"The effect of food on the pharmacokinetics of oral ivermectin","volume":"75","author":"Duthaler U","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000236"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008886"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1456"},{"key":"e_1_2_10_39_1","first-page":"361","article-title":"Ivermectin dose assessment without weighing scales","volume":"71","author":"Alexander N","year":"1993","journal-title":"Bull World Health Organ"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-11-111"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.13038","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T19:00:29Z","timestamp":1704049229000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.13038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,11]]},"references-count":39,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1002\/psp4.13038"],"URL":"https:\/\/doi.org\/10.1002\/psp4.13038","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,11]]},"assertion":[{"value":"2023-04-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}