{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:28:59Z","timestamp":1787016539343,"version":"build-2736575974"},"reference-count":19,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Merck &amp; Co., Inc."}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,4,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>The objective of this study was to support posaconazole dose regimens in pediatric patients aged \u22652 years, using a population pharmacokinetic (PK) approach with data from a phase 1b study (NCT02452034). A one-compartment model with first-order absorption was fit to pharmacokinetic data from 144 participants aged 2 to 17 years, who were administered posaconazole as intravenous (IV) and powder for oral suspension (PFS) formulations, or IV only, at dosing regimens of 3.5, 4.5, and 6 mg\/kg. The influence of demographic and clinical factors on pharmacokinetic parameters was evaluated using a stepwise forward inclusion\/backward exclusion procedure. The final model simulated posaconazole exposure in patients aged 2 to &lt;7 and 7 to 17 years at dosing regimens of 4.5, 6, and 7.5 mg\/kg. Plasma concentration data following IV and PFS administration were well-described by a one-compartment model with first-order absorption and estimated bioavailability, where clearance and volume were subject to allometric scaling by body weight. The 6-mg\/kg dosing regimen achieved the pharmacokinetic target (90% of the pediatric population having an average steady-state plasma concentration of \u2265500 and &lt;2,000 ng\/mL) for both age groups, regardless of whether patients received IV and PFS or IV only. In a virtual adolescent population (body weight &gt;40 kg), the 300 mg\/day posaconazole tablet was also predicted to achieve the pharmacokinetic target and remain within a safe range of exposure. These data informed a weight-based nomogram for PFS dosing to maximize the number of pediatric patients achieving the pharmacokinetic target across weight bands, while also maintaining a favorable benefit\/risk profile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01197-23","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T09:10:51Z","timestamp":1708420251000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["A population pharmacokinetic model for posaconazole intravenous solution and oral powder for suspension formulations in pediatric patients with neutropenia"],"prefix":"10.1128","volume":"68","author":[{"given":"Gregory","family":"Winchell","sequence":"first","affiliation":[{"name":"Certara USA, Inc., Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik","family":"de Greef","sequence":"additional","affiliation":[{"name":"Certara USA, Inc., Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz","family":"Ouerdani","sequence":"additional","affiliation":[{"name":"Certara France, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris","family":"Fauchet","sequence":"additional","affiliation":[{"name":"Certara France, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-8326","authenticated-orcid":false,"given":"Rebecca E.","family":"Wrishko","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Mangin","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Bruno","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetty","family":"Waskin","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Rahway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/588660"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/10245330512331390023"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.inf.0000220256.69385.2e"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1702654"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1705113"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.mph.0000155861.38641.ca"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/08998280.2007.11928283"},{"key":"e_1_3_4_9_2","volume-title":"NOXAFIL (posaconazole) injection, for intravenous use. NOXAFIL (posaconazole) delayed-release tablets, for oral use. NOXAFIL (posaconazole) oral suspension","year":"2022","unstructured":"2022. NOXAFIL (posaconazole) injection, for intravenous use. NOXAFIL (posaconazole) delayed-release tablets, for oral use. NOXAFIL (posaconazole) oral suspension. Merck Sharp & Dohme LLC, Rahway, NJ, USA."},{"key":"e_1_3_4_10_2","volume-title":"Noxafilr (posaconazole) tablets and oral suspension 40 mg\/mL","year":"2022","unstructured":"2022. Noxafilr (posaconazole) tablets and oral suspension 40 mg\/mL. 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Available from: https:\/\/wwwn.cdc.gov\/nchs\/nhanes\/search\/datapage.aspx?Component=Demographics"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01197-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01197-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T09:07:52Z","timestamp":1712135272000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01197-23"}},"subtitle":[],"editor":[{"given":"Damian J.","family":"Krysan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,3]]},"references-count":19,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4,3]]}},"alternative-id":["10.1128\/aac.01197-23"],"URL":"https:\/\/doi.org\/10.1128\/aac.01197-23","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,3]]},"assertion":[{"value":"2023-09-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01197-23"}}