{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:45:52Z","timestamp":1766159152235},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T00:00:00Z","timestamp":1686960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010877","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":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fostemsavir, a prodrug of the first\u2010in\u2010class HIV\u20101 attachment inhibitor temsavir, is approved for the treatment of multidrug\u2010resistant HIV\u20101 in adults; its use in pediatric populations is currently being studied. Population pharmacokinetic modeling across pediatric weight bands was used to guide pediatric fostemsavir dose selection. Dosing simulations demonstrated that twice\u2010daily fostemsavir 600\u2010mg (adult dose) and 400\u2010mg doses met safety and efficacy criteria for 35\u00a0kg or greater and 20 or greater to less than 35\u00a0kg pediatric weight bands, respectively. Temsavir relative bioavailability of 2 low\u2010dose fostemsavir extended\u2010release\u00a0formulations (3\u00a0\u00d7\u00a0200\u00a0mg; formulations A and B) and reference formulation (600\u00a0mg extended release) was assessed in a 2\u2010part, open\u2010label, randomized, crossover study in healthy adults. Part 1 (<jats:italic>N<\/jats:italic>\u00a0=\u00a032) compared single\u2010dose temsavir relative bioavailability, and Part 2 (<jats:italic>N<\/jats:italic>\u00a0=\u00a016) evaluated the impact of fed versus fasted conditions using the selected low\u2010dose formulation. Temsavir geometric mean ratios for the area under the plasma concentration\u2013time curve from time zero to infinity and maximum concentration for formulation B were bioequivalent to the reference formulation. Temsavir maximum concentration for formulation B was similar in fed and fasted states, but area under the plasma concentration\u2013time curve from time zero to infinity geometric mean ratio was increased under fed conditions, consistent with previous results in adults. These analyses demonstrated efficient pediatric dose selection using a model\u2010based approach.<\/jats:p>","DOI":"10.1002\/cpdd.1291","type":"journal-article","created":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T10:34:31Z","timestamp":1686998071000},"page":"991-1000","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Model\u2010Based Dose Selection of Fostemsavir for Pediatric Populations With Multidrug\u2010Resistant HIV\u20101 and Relative Bioavailability Assessment in Healthy Adults"],"prefix":"10.1002","volume":"12","author":[{"given":"Nilay","family":"Thakkar","sequence":"first","affiliation":[{"name":"GSK  Collegeville PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mindy","family":"Magee","sequence":"additional","affiliation":[{"name":"GSK  Collegeville PA 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,6,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/20469047.2020.1853350"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.7448\/IAS.18.7.20270"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40471-021-00268-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60208-0"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw213"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000001843"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1902493"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23476"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2022.2119179"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02251-21"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04914-14"},{"key":"e_1_2_7_13_1","unstructured":"SevinskyH MageeM AckermanP et\u00a0al.The effect of food on the pharmacokinetics of the HIV\u20101 attachment inhibitor temsavir the active moiety of the prodrug fostemsavir.Presented at: 18th International Workshop on Clinical Pharmacology of Antiviral Therapy;2017;Chicago IL."},{"issue":"1","key":"e_1_2_7_14_1","first-page":"1","article-title":"Evaluation of the pharmacokinetic drug\u2010drug interaction between the antiretroviral agents fostemsavir and maraviroc: a single\u2010sequence crossover study in healthy participants","volume":"23","author":"Wire MB","year":"2021","journal-title":"HIV Res Clin 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