{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:07:08Z","timestamp":1753870028064,"version":"3.41.2"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T00:00:00Z","timestamp":1746316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fostemsavir (FTR, GSK3684934; formerly BMS\u2010663068) is a human immunodeficiency virus type 1 (HIV\u20101) attachment inhibitor approved for the treatment of multidrug\u2010resistant HIV\u20101 infection in heavily treatment\u2010experienced (HTE) patients failing their current antiretroviral regimen. FTR is an extended\u2010release prodrug and is hydrolyzed by alkaline phosphatase in the gastrointestinal lumen to its active moiety, temsavir (TMR). TMR is primarily metabolized by esterase\u2010mediated hydrolysis with contributions from cytochrome P450 (CYP) 3A4. A population pharmacokinetic (PK) analysis was performed using TMR exposure data from seven clinical studies (Phases 1 through 3) to characterize the time course of TMR plasma concentrations and to evaluate covariate effects on TMR PK. This analysis showed TMR PK was adequately described using a two\u2010compartment model with dual zero and first\u2010order absorption and first\u2010order elimination with CYP3A inducers and inhibitors as covariates on CL\/F and allometrically scaled body weight as a covariate on CL\/F, V2\/F, Q\/F, and V3\/F. Exposure metrics were derived from the final population PK model to assess relationships between TMR PK and efficacy at Day 8 and Week 24 and safety endpoints of interest, using exposure\u2010response (ER) models. Both the population PK and E\u2010R models support administration of FTR 600\u2009mg BID to decrease virologic load in HIV\u20101 HTE patients, with no dose adjustments necessary for coadministration with moderate CYP3A inducers, strong CYP3A inhibitors, prandial status, or body weight. Results from this analysis supported the regulatory approval of the fostemsavir 600\u2009mg dose and are applicable to clinical trial simulations in other scenarios and populations (e.g., pediatrics).<\/jats:p>","DOI":"10.1002\/prp2.70023","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T06:20:35Z","timestamp":1746426035000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetics and exposure\u2010response relationship for temsavir following fostemsavir administration in treatment\u2010experienced <scp>HIV<\/scp> patients"],"prefix":"10.1002","volume":"13","author":[{"given":"Ridhi","family":"Parasrampuria","sequence":"first","affiliation":[{"name":"GlaxoSmithKline  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2846-5796","authenticated-orcid":false,"given":"Nilay","family":"Thakkar","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katy","family":"Moore","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Ackerman","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Branford Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mindy","family":"Magee","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,4]]},"reference":[{"volume-title":"Global HIV & Aids Statistics\u20142020 Fact Sheet","year":"2020","author":"UNAIDS","key":"e_1_2_12_2_1"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199803263381301"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/420789"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.24726"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01337"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23476"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00513-13"},{"key":"e_1_2_12_9_1","unstructured":"NettlesR ChienC ElefantE et\u00a0al.Single and multiple dose pharmacokinetics and safety in non\u2010HIV\u2010infected health subjects dosed with BMS\u2010663068 an oral HIV attachment inhibitor.2011. Presented At: 12th Int Workshop on Clin Pharmacology of HIV Therapy Miami FL USA."},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02251-21"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04914-14"},{"key":"e_1_2_12_12_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.2017. Abstr 18th International Workshop on Clinical Pharmacology of Antiviral Therapy Chicago IL June 14\u201316."},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02503-15"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12763"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis432"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(15)00177-0"},{"key":"e_1_2_12_17_1","first-page":"31","article-title":"Fostemsavir in heavily treatment\u2010experienced individuals living with HIV\u20101: insights from the phase 3 BRIGHTE study","volume":"3","author":"Lataillade M","year":"2021","journal-title":"J Aids Hiv Treat"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1810"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1997.tb04326.x"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.70023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T10:19:31Z","timestamp":1750155571000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.70023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,4]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/prp2.70023"],"URL":"https:\/\/doi.org\/10.1002\/prp2.70023","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"type":"print","value":"2052-1707"},{"type":"electronic","value":"2052-1707"}],"subject":[],"published":{"date-parts":[[2025,5,4]]},"assertion":[{"value":"2024-05-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70023"}}