{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:18:35Z","timestamp":1791512315147,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,8]],"date-time":"2024-12-08T00:00:00Z","timestamp":1733616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Islatravir is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment of HIV\u20101. People living with HIV\u20101 receiving methadone maintenance therapy may benefit from islatravir. This study was designed to evaluate single\u2010dose islatravir on steady\u2010state methadone pharmacokinetics. A nonrandomized, open\u2010label study (NCT04568603) was conducted and included adult participants receiving methadone therapy. Participants received their standard methadone therapy and a single oral dose of islatravir 60\u00a0mg concomitantly. Blood samples were collected to determine methadone and islatravir pharmacokinetics. Fourteen participants aged 26\u201063\u00a0years were enrolled; 13 completed the study. The geometric mean ratios for methadone area under the concentration\u2010time curve from time 0 to 24\u00a0hours (AUC<jats:sub>0\u201024<\/jats:sub>), maximum plasma concentration (C<jats:sub>max<\/jats:sub>), and concentration at 24\u00a0hours (C<jats:sub>24<\/jats:sub>) were 1.03, 1.01, and 1.07, respectively. Similar effects were seen for the R\u2010 and S\u2010enantiomer of methadone (R\u2010methadone: AUC<jats:sub>0\u201024<\/jats:sub>, 1.03; C<jats:sub>max<\/jats:sub>, 1.02; and C<jats:sub>24<\/jats:sub>, 1.06; S\u2010methadone: AUC<jats:sub>0\u201024<\/jats:sub>, 1.03; C<jats:sub>max<\/jats:sub>, 1.01; and C<jats:sub>24<\/jats:sub>, 1.08). For islatravir, based on a comparison with historical data, the geometric mean ratios for AUC<jats:sub>0\u2010inf<\/jats:sub> and C<jats:sub>max<\/jats:sub> were 1.18 and 0.86, respectively. Coadministration of a single dose of islatravir and methadone was generally well tolerated. Single\u2010dose islatravir did not affect steady\u2010state methadone pharmacokinetics in a clinically meaningful way.<\/jats:p>","DOI":"10.1002\/cpdd.1492","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T07:16:17Z","timestamp":1733728577000},"page":"36-43","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Phase 1 Study to Evaluate the Pharmacokinetic Drug\u2010Drug Interaction Between Islatravir and Methadone in Participants on Stable Methadone Therapy"],"prefix":"10.1002","volume":"14","author":[{"given":"Randolph P.","family":"Matthews","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Ankrom","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  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Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-021-01046-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.04.007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13048"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1605223113"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.562694"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000599"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002755"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13081566"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(21)00021-7"},{"key":"e_1_2_10_11_1","unstructured":"SquiresK CorrellTA RobertsonMN et\u00a0al.Effect of islatravir on total lymphocyte and lymphocyte subst counts.Presented at the Conference on Retroviruses and Opportunistic Infections (CROI) Seattle Washington; February 19\u201022 2023. Accessed May 14 2024. Available at:https:\/\/www.croiconference.org\/abstract\/effect\u2010of\u2010islatravir\u2010on\u2010total\u2010lymphocyte\u2010and\u2010lymphocyte\u2010subset\u2010counts\/"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002879"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(19)30372-8"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2018.08.025"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241140-00003"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12687"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.137"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1427"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3181642938"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1405"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4637.2009.00596.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-200007010-00008"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042560-199808150-00004"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00931-22"},{"key":"e_1_2_10_25_1","volume-title":"Table for Grading the Severity of Adult and Pediatric Adverse Events","author":"U.S. Department of Health and Human Services"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13048"},{"key":"e_1_2_10_27_1","unstructured":"SquiresKE CorrellTA RobertsonMN et\u00a0al.Effect of islatravir on total lymphocyte and lymphocyte subst counts.Presented at the Conference on Retroviruses and Opportunistic Infections (CROI) Seattle Washington; February 19\u201022 2023.https:\/\/www.croiconference.org\/abstract\/effect\u2010of\u2010islatravir\u2010on\u2010total\u2010lymphocyte\u2010and\u2010lymphocyte\u2010subset\u2010counts\/"},{"key":"e_1_2_10_28_1","unstructured":"ClinicalTrials.gov.NCT05052996: Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in VirologicallySuppressed People With HIV. 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