{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:10:02Z","timestamp":1707351002857},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"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":[[2024,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This phase I study investigated potential drug\u2013drug interactions of the maturation inhibitor GSK3640254 (GSK'254) with darunavir\/ritonavir (DRV\/RTV) and\/or etravirine (ETR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this randomized, open\u2010label, single\u2010sequence, multiple\u2010dose study, healthy participants received GSK'254 200\u2009mg once daily alone or coadministered with DRV\/RTV 600\/100\u2009mg twice daily (BID; <jats:italic>n<\/jats:italic>\u2009=\u200919), ETR 200\u2009mg BID (<jats:italic>n<\/jats:italic>\u2009=\u200919) or DRV\/RTV 600\/100\u2009mg\u2009+\u2009ETR 200\u2009mg BID (<jats:italic>n<\/jats:italic>\u2009=\u200916) under fed conditions. Primary endpoints were steady\u2010state area under the plasma concentration\u2013time curve from time 0 to the end of the dosing interval (AUC<jats:sub>0\u2010\u03c4<\/jats:sub>) and maximum observed concentration (C<jats:sub>max<\/jats:sub>). Secondary endpoints included trough concentration (C<jats:sub>\u03c4<\/jats:sub>), safety and tolerability. Pharmacokinetic parameters were calculated using standard noncompartmental analysis, and geometric least\u2010squares mean ratios were derived from linear mixed\u2010effects models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GSK'254 AUC<jats:sub>0\u2010\u03c4<\/jats:sub> (geometric least\u2010squares mean ratio [90% confidence interval], 1.14 [1.00\u20131.29]), C<jats:sub>max<\/jats:sub> (1.07 [0.92\u20131.24]) and C<jats:sub>\u03c4<\/jats:sub> (1.17 [1.01\u20131.35]) were similar when administered alone and with DRV\/RTV. Etravirine coadministration decreased GSK'254 AUC<jats:sub>0\u2010\u03c4<\/jats:sub> (0.53 [0.48\u20130.59]), C<jats:sub>max<\/jats:sub> (0.60 [0.53\u20130.68]) and C<jats:sub>\u03c4<\/jats:sub> (0.51 [0.39\u20130.66]). Similar reductions were not observed with GSK'254\u2009+\u2009DRV\/RTV\u2009+\u2009ETR (AUC<jats:sub>0\u2010\u03c4<\/jats:sub>, 0.94 [0.82\u20131.09]; C<jats:sub>max<\/jats:sub>, 0.89 [0.75\u20131.07]; C<jats:sub>\u03c4<\/jats:sub>, 1.02 [0.89\u20131.18]). GSK'254 had no meaningful effect on DRV\/RTV or ETR concentrations. All reported adverse events (AEs) were grade 1; 3 led to withdrawal and resolved (rash, asymptomatic electrocardiogram T\u2010wave inversion, periorbital oedema). Most common AEs were diarrhoea (<jats:italic>n<\/jats:italic>\u2009=\u20099) and headache (<jats:italic>n<\/jats:italic>\u2009=\u20097). No deaths or serious AEs occurred.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>GSK'254 pharmacokinetics was not meaningfully affected by DRV\/RTV or DRV\/RTV\u2009+\u2009ETR, but were reduced with only ETR; no new tolerability concerns were observed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15893","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T04:37:38Z","timestamp":1692938258000},"page":"274-285","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and tolerability of the maturation inhibitor GSK3640254 coadministered with darunavir\/ritonavir and\/or etravirine in healthy adults"],"prefix":"10.1111","volume":"90","author":[{"given":"Ying","family":"Zhang","sequence":"first","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samit","family":"Joshi","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Branford Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parto","family":"Yazdani","sequence":"additional","affiliation":[{"name":"GSK  Mississauga Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce","family":"Zhan","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Wen","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Bainbridge","sequence":"additional","affiliation":[{"name":"GSK  Brentford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Ballesteros\u2010Perez","sequence":"additional","affiliation":[{"name":"Certara  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Gartland","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Lataillade","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Branford Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku112"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz237"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000849"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0160087"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2021.106406"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2015.05.004"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2019.1604685"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.339374"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5398.80"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3503"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.11.5667\u20105677.2002"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.11.002"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01926\u201010"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001215"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01876\u201021"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.01.013"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.671"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab1065"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15051"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14759"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02173\u201020"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1051"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32834a1dd9"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.122.000955"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15699"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.22246"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010019\u201000830\u20109"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010693107"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx459"},{"key":"e_1_2_11_31_1","unstructured":"Intelence [package insert]. 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