{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:49:37Z","timestamp":1791528577695,"version":"4.3.4"},"reference-count":18,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020956","name":"Merck Healthcare KGaA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020956","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Schistosomiasis is an acute and chronic parasitic disease that occurs mainly in sub\u2010Saharan and African countries and for which no treatment is available in preschool\u2010aged children (PSAC). An open\u2010label, Phase III study of arpraziquantel pediatric formulation evaluated safety and efficacy in 280\n                    <jats:italic>Schistosoma<\/jats:italic>\n                    \u2010infected PSAC (NCT03845140). A population pharmacokinetics (PK) model for arpraziquantel and its active metabolite trans\u20104\u2010hydroxy\u2010arpraziquantel was developed from concentration measurements (from n = 74 and n = 30 children for arpraziquantel and its metabolite, respectively) after a single dose of 50 or 60\u00a0mg\/kg arpraziquantel. Extensive PK variability was observed but no significant covariates were identified in the final model other than body weight. Body weight\u2010normalized apparent clearances overlapped across all weight and age categories, supporting body weight\u2010based dosing. No apparent relationship was discernible between an efficacious response and arpraziquantel and\/or trans\u20104\u2010hydroxy\u2010arpraziquantel exposures. Logistic regression analysis indicated higher incidence of treatment\u2010emergent adverse events (TEAEs) with increasing arpraziquantel exposure. For gastrointestinal TEAEs, the incidence was related to infection type with higher incidence in\n                    <jats:italic>Schistosoma mansoni<\/jats:italic>\n                    \u2010infected children. These population PK and exposure\u2013response analyses performed after administration of arpraziquantel pediatric formulation support the weight\u2010based dosing bands posology and the consistency in therapeutic effect over the range of exposures observed in PSAC.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.70106","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:00:16Z","timestamp":1791525616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics and Exposure\u2013Response Analysis of Arpraziquantel Supporting Dose in Preschool\u2010Aged Children Infected with\n                    <i>Schistosoma<\/i>"],"prefix":"10.1002","volume":"15","author":[{"given":"Brigitte","family":"Brockhaus","sequence":"first","affiliation":[{"name":"The Healthcare Business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Mills","sequence":"additional","affiliation":[{"name":"ICON Clinical Research Limited South County Business Park Leopardstown  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u2010Marija","family":"Milenkovi\u0107\u2010Gri\u0161i\u0107","sequence":"additional","affiliation":[{"name":"The Healthcare Business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"B\u00f6dding","sequence":"additional","affiliation":[{"name":"The Healthcare Business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Strotmann","sequence":"additional","affiliation":[{"name":"The Healthcare Business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelmina","family":"Bagchus","sequence":"additional","affiliation":[{"name":"Merck Institute of Pharmacometrics Lausanne, Switzerland, An Affiliate of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet R.","family":"Wade","sequence":"additional","affiliation":[{"name":"Occams Co\u00f6peratie U.A.  Amstelveen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gao","sequence":"additional","affiliation":[{"name":"EMD Serono Research and Development Institute Inc., An Affiliate of Merck KGaA Darmstadt, Germany Billerica  MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Venkatakrishnan","sequence":"additional","affiliation":[{"name":"EMD Serono Research and Development Institute Inc., An Affiliate of Merck KGaA Darmstadt, Germany Billerica  MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathej","family":"Gopalakrishnan","sequence":"additional","affiliation":[{"name":"The Healthcare Business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Khandelwal","sequence":"additional","affiliation":[{"name":"The Healthcare Business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World Health Organization.Schistosomiasis. Key facts. Geneva: World Health Organization; 2023.https:\/\/www.who.int"},{"key":"e_1_2_11_3_1","unstructured":"World Health Organization.Health topics: Schistosomiasis (Bilharzia). Geneva: World Health Organization; 2023.https:\/\/www.who.int"},{"issue":"5","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"862","DOI":"10.4269\/ajtmh.2012.12-0248","article-title":"Mechanism of anemia in Schistosoma mansoni\u2013infected school children in Western Kenya","volume":"87","author":"Butler SE","year":"2012","journal-title":"Am J Trop Med Hyg"},{"issue":"5","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"332","DOI":"10.5581\/1516-8484.20130098","article-title":"Relationship between splenomegaly and hematologic findings in patients with hepatosplenic schistosomiasis","volume":"35","author":"Leite LA","year":"2013","journal-title":"Rev Bras Hematol Hemoter"},{"issue":"12","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0244695","article-title":"A systematic review and meta\u2010analysis quantifying schistosomiasis infection burden in pre\u2010school aged children (PreSAC) in sub\u2010Saharan Africa for the period 2000\u20102020","volume":"15","author":"Kalinda C","year":"2020","journal-title":"PLoS One"},{"key":"e_1_2_11_7_1","unstructured":"World Health Organization.Guideline on control and elimination of human schistosomiasis [Internet]. Geneva: World Health Organization; 2022.https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/351856\/9789240041608\u2010eng.pdf?sequence=1"},{"issue":"625","key":"e_1_2_11_8_1","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abj5832","article-title":"Mechanism of praziquantel action at a parasitic flatworm ion channel","volume":"13","author":"Park SK","year":"2021","journal-title":"Sci Transl Med"},{"issue":"7","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/S1473-3099(23)00048-8","article-title":"Efficacy, safety, palatability or arpraziquantel (L\u2010praziquantel) orodispersible tablets in children aged 3 months to 6 years infected with Schistosoma in C\u00f4te d'Ivoire and Kenya: an open\u2010label, partly randomized, phase 3 trial","volume":"23","author":"N'Goran EK","year":"2023","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/cts.12601","article-title":"Relative bioavailability of orally dispersible tablet formulations of levo\u2010 and racemic praziquantel: two phase I studies","volume":"12","author":"Bagchus WM","year":"2019","journal-title":"Clin Transl Sci"},{"issue":"5","key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s10928-007-9066-0","article-title":"Implementation of a transit compartment model for describing drug absorption in pharmacokinetic studies","volume":"34","author":"Savic RM","year":"2007","journal-title":"J Pharmacokinet Pharmacodyn"},{"key":"e_1_2_11_12_1","unstructured":"BauerRJ.Nonmem Users Manual introduction to NONMEM 7.5.0.ICON plc;2020. p.181.https:\/\/nonmem.iconplc.com\/nonmem750\/nm750.pdf"},{"issue":"4","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.pt.2013.02.001","article-title":"Schistosomiasis in African infants and preschool children: let them now be treated!","volume":"29","author":"Stothard JR","year":"2013","journal-title":"Trends Parasitol"},{"issue":"1","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s40249-017-0300-8","article-title":"Putting the treatment of paediatric schistosomiasis into context","volume":"6","author":"Mduluza T","year":"2017","journal-title":"Infect Dis Poverty"},{"key":"e_1_2_11_15_1","unstructured":"Pediatric Praziquantel Consortium. Accessed February 3 2023.https:\/\/www.pediatricpraziquantelconsortium.org\/"},{"issue":"3","key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s10928-021-09791-8","article-title":"R\u2010praziquantel integrated population pharmacokinetics in preschool\u2010and school\u2010aged African children infected with Schistosoma mansoni and S. haematobium and Lao adults infected with Opisthorchis viverrini","volume":"49","author":"Falcoz C","year":"2022","journal-title":"J Pharmacokinet Pharmacodyn"},{"issue":"5","key":"e_1_2_11_17_1","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s10928-018-9601-1","article-title":"Extrapolation of praziquantel pharmacokinetics to a pediatric population: a cautionary tale","volume":"45","author":"Bonate PL","year":"2018","journal-title":"J Pharmacokinet Pharmacodyn"},{"issue":"8","key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"e02253","DOI":"10.1128\/AAC.02253-17","article-title":"Pharmacokinetics of praziquantel in Schistosoma mansoni\u2010 and Schistosoma haematobium\u2010infected school\u2010 and preschool\u2010aged children","volume":"62","author":"Kova\u010d J","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"e327","DOI":"10.1016\/S1473-3099(22)00221-3","article-title":"Review of 2022 WHO guidelines on the control and elimination of schistosomiasis","volume":"22","author":"Lo NC","year":"2022","journal-title":"Lancet Infect Dis"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70106","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.70106","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:00:19Z","timestamp":1791525619000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.70106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":18,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/cpdd.70106"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.70106","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70106"}}