{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T23:08:07Z","timestamp":1724886487517},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"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":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>GSK3640254 is a next\u2010generation maturation inhibitor likely to be coadministered with combined oral contraceptives in HIV\u2010positive women.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This phase I, open\u2010label, 1\u2010way study assessed pharmacokinetic and pharmacodynamic interactions of GSK3640254 200\u2009mg and ethinyl oestradiol 0.03\u2009mg\/levonorgestrel 0.15\u2009mg once daily in healthy female participants who received ethinyl oestradiol\/levonorgestrel for 10\u00a0days with a moderate\u2010fat meal after which GSK3640254 was added from Days 11 to 21. Primary endpoints were area under the plasma concentration\u2013time curve to the end of the dosing interval (AUC<jats:sub>0\u2010t<\/jats:sub>), maximum observed concentration (C<jats:sub>max<\/jats:sub>) and plasma concentration at the end of the dosing interval (C<jats:sub>\u03c4<\/jats:sub>) for ethinyl oestradiol and levonorgestrel. Serum follicle\u2010stimulating hormone, luteinizing hormone and progesterone concentrations were determined. Adverse events were monitored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 23 enrolled participants, 17 completed the study. Geometric least squares mean ratios (with <jats:italic>vs<\/jats:italic>. without GSK3640254) of AUC<jats:sub>0\u2010t<\/jats:sub>, C<jats:sub>max<\/jats:sub> and C<jats:sub>\u03c4<\/jats:sub> were 0.974, 0.970 and 1.050 for ethinyl oestradiol and 1.069, 1.032 and 1.083 for levonorgestrel, respectively. Three participants had elevated progesterone levels, which occurred before GSK3640254 administration in 2 participants. No participants had elevated follicle\u2010stimulating hormone or luteinizing hormone values. Fourteen participants (61%) reported adverse events. Four participants reported asymptomatic elevated transaminase levels meeting liver\u2010stopping criteria; of these, 3 events occurred before GSK3640254 administration and led to study withdrawal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Ethinyl oestradiol\/levonorgestrel plus GSK3640254 coadministration did not affect steady\u2010state pharmacokinetics or pharmacodynamics of ethinyl oestradiol and levonorgestrel in healthy female participants. No major tolerability findings were reported. Elevated liver transaminase levels were probably due to ethinyl oestradiol\/levonorgestrel.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15051","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T15:03:52Z","timestamp":1629817432000},"page":"1704-1712","source":"Crossref","is-referenced-by-count":5,"title":["Lack of pharmacokinetic interaction between the HIV\u20101 maturation inhibitor GSK3640254 and combination oral contraceptives in healthy women"],"prefix":"10.1111","volume":"88","author":[{"given":"Teodora","family":"Pene Dumitrescu","sequence":"first","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Greene","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samit R.","family":"Joshi","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Branford CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Johnson","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Research Triangle Park  NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona","family":"Halliday","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Uxbridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurie","family":"Butcher","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"PPD  Richmond VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey","family":"Webster","sequence":"additional","affiliation":[{"name":"PPD  Richmond VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa T.","family":"Pham","sequence":"additional","affiliation":[{"name":"PPD  Austin TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Lataillade","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Branford CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherene","family":"Min","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, Research Triangle Park  NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a007161"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0205368"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2015.05.004"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2234683100"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00152-07"},{"issue":"3","key":"e_1_2_14_7_1","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1093\/cid\/cix239","article-title":"Antiviral activity, safety, and exposure\u2010response relationships of GSK3532795, a second\u2010generation human immunodeficiency virus type 1 maturation inhibitor, administered as monotherapy or in combination with atazanavir with or without ritonavir in a phase 2a randomized, dose\u2010ranging, controlled trial (AI468002)","volume":"65","author":"Hwang C","year":"2017","journal-title":"Clin Infect Dis"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02560-15"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz938"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.671"},{"key":"e_1_2_14_11_1","unstructured":"United Nations Department of Economic and Social Affairs.Contraceptive Use by Method 2019.https:\/\/www.un.org\/development\/desa\/pd\/sites\/www.un.org.development.desa.pd\/files\/files\/documents\/2020\/Jan\/un_2019_contraceptiveusebymethod_databooklet.pdf. 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