{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:35:23Z","timestamp":1790127323430,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T00:00:00Z","timestamp":1559692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"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":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Regional human immunodeficiency virus (HIV) prevalence rates are high in people with history of injection drug use, including those managed with maintenance opioids. Fostemsavir (FTR) is an oral prodrug of temsavir, a first\u2010in\u2010class attachment inhibitor that binds HIV\u20101 gp120, preventing initial HIV attachment and entry into host immune cells. Here we determine the impact of FTR on the pharmacokinetics of opioids methadone (MET: <jats:italic>R<\/jats:italic>\u2010, <jats:italic>S<\/jats:italic>\u2010 and total) or buprenorphine and norbuprenorphine (BUP and norBUP) when coadministered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Study 206216 (NCT02666001) was a Phase I, open\u2010label study, assessing the effect of FTR 600\u00a0mg (extended\u2010release formulation) twice daily on pharmacokinetics of MET or BUP and norBUP, in non\u2010HIV\u2010infected participants on stable maintenance therapy with MET (40\u2013120\u00a0mg; <jats:italic>n<\/jats:italic>\u00a0=\u00a016) or BUP plus naloxone (8\u201324\u00a0mg plus 2\u20136\u00a0mg; <jats:italic>n<\/jats:italic>\u00a0=\u00a016); pharmacodynamic response was assessed using standard opioid rating scales.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following coadministration with FTR, dose\u2010normalized MET (<jats:italic>R\u2010, S\u2010<\/jats:italic> and total) exposures (maximum concentration in plasma, area under the plasma concentration\u2013time curve over the dosing interval and concentration in plasma at 24\u00a0hours) increased 9\u201315% and BUP and norBUP exposures increased 24\u201339%. The 90% confidence interval ranges for MET (1.01\u20131.21) and BUP and norBUP (1.03\u20131.69) were within respective no\u2010effect ranges (0.7\u20131.43 and 0.5\u20132.0). Opioid pharmacodynamic scores were similar with and without MET\/BUP with no symptoms of withdrawal\/overdose; no new safety signal for FTR when combined with a stable opioid regimen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>FTR did not impact MET and had no clinically significant impact on BUP pharmacokinetics. Standardized assessments of opioid pharmacodynamics were unchanged throughout FTR administration with MET or BUP. FTR can be administered with MET or BUP without dose adjustment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13964","type":"journal-article","created":{"date-parts":[[2019,4,13]],"date-time":"2019-04-13T18:13:27Z","timestamp":1555179207000},"page":"1771-1780","source":"Crossref","is-referenced-by-count":12,"title":["Methadone and buprenorphine pharmacokinetics and pharmacodynamics when coadministered with fostemsavir to opioid\u2010dependent, human immunodeficiency virus seronegative participants"],"prefix":"10.1111","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7838-381X","authenticated-orcid":false,"given":"Katy","family":"Moore","sequence":"first","affiliation":[{"name":"ViiV Healthcare  RTP NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mindy","family":"Magee","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Upper Providence PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Sevinsky","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Upper Providence PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Chang","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Hopewell NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Lubin","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Hopewell NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Myers","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Hopewell NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ackerman","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Branford CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Llamoso","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Branford CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2010.09.012"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1521-0391.2009.00005.x"},{"key":"e_1_2_9_4_1","unstructured":"World Health Organization.People who inject drugs (PWID).2017.https:\/\/www.who.int\/hiv\/topics\/idu\/en\/. 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