{"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":1791512315694,"version":"4.3.4"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Merck","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,2,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The development of new and improved antiretroviral therapies that allow for alternative dosing schedules is needed for people living with HIV-1. Islatravir is a deoxyadenosine analog in development for the treatment of HIV-1 that suppresses HIV-1 replication via multiple mechanisms of action, including reverse transcriptase translocation inhibition and delayed chain termination. Islatravir is differentiated from other HIV-1 antiretrovirals by its high potency, long\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>\u00bd<\/jats:sub>\n                      , broad tissue distribution, and favorable drug resistance profile. A comprehensive evaluation was performed to provide data on the mass balance, absorption, metabolism, and excretion of islatravir through studies in nonclinical species, and in adults without HIV-1 infection, using radiolabeled islatravir. Islatravir was well absorbed in both nonclinical species and humans following oral administration. The elimination of islatravir occurs primarily by a combination of oxidative deamination to 4\u2032-ethynyl-2-fluoro-2\u2032-deoxyinosine and renal excretion of unchanged islatravir. Islatravir and 4\u2032-ethynyl-2-fluoro-2\u2032-deoxyinosine are the major circulating drug components in all species assessed. Islatravir is readily taken up into cells with efficient phosphorylation to the mono-, di-, and triphosphate forms. The pharmacologically active islatravir triphosphate is the most abundant intracellular phosphorylated species, as shown by the results of\n                      <jats:italic>ex vivo<\/jats:italic>\n                      studies. This characterization of the absorption, metabolism, and elimination of islatravir in humans and nonclinical species supports its further development for the treatment of HIV-1.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01030-24","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T09:00:34Z","timestamp":1736845234000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Nonclinical and clinical characterization of the absorption, metabolism, and excretion of islatravir"],"prefix":"10.1128","volume":"69","author":[{"given":"Kerry L.","family":"Fillgrove","sequence":"first","affiliation":[{"name":"Merck & Co., Inc","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8403-267X","authenticated-orcid":true,"given":"Randolph P.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Lu","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexia","family":"Liang","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6892-0899","authenticated-orcid":false,"given":"Munjal","family":"Patel","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Z.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Aubrey","family":"Stoch","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa I.","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc","place":["Rahway, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"WHO. 2023. Global HIV programme. Available from: https:\/\/www.who.int\/teams\/global-hiv-hepatitis-and-stis-programmes\/hiv\/treatment#:~:text=The%20main%20objective%20of%20treatment life%20and%20preventing%20HIV%20transmission. Retrieved 2 Jan 2025."},{"key":"e_1_3_4_3_2","unstructured":"DHHS. 2023. Department of health and human services. Panel on antiretroviral guidelines for adults and adolescents guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Available from: https:\/\/clinicalinfo.hiv.gov\/sites\/default\/files\/guidelines\/documents\/adult-adolescent-arv\/guidelines-adult-adolescent-arv.pdf. Retrieved 2 Jan 2025."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13048"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(21)00021-7"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00133-22"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002879"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.04.007"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1605223113"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.562694"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(19)30372-8"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000599"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/v13081566"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002755"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2021.03.004"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00931-22"},{"key":"e_1_3_4_17_2","unstructured":"The human protein atlas. 2024. Available from: https:\/\/www.proteinatlas.org\/ENSG00000196839-ADA\/tissue. Retrieved 2 Jan 2025."},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-406x(65)90011-3"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac015"},{"key":"e_1_3_4_20_2","unstructured":"Squires K Correll TA Robertson MN Klopfer SO Hwang PM Zhou Y-P Martin E Rhee E. 2023. Effect of islatravir on total lymphocyte and lymphocyte subset counts. Conference on Retroviruses and Opportunistic Infections (CROI). Available from: https:\/\/www.croiconference.org\/abstract\/effect-of-islatravir-on-total-lymphocyte-and-lymphocyte-subset-counts. Retrieved 2 Jan 2025."},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(24)00030-4"},{"key":"e_1_3_4_22_2","volume-title":"Presented at: 12th IAS Conference on HIV Science; July 23-26, 2023","author":"Squires K","unstructured":"Squires K, Correll TA, Robertson MN. Incidence of infections across islatravir clinical development programs. Presented at: 12th IAS Conference on HIV Science; July 23-26, 2023. , Brisbane, Australia"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1981.56"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01236-10"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01479-3"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01030-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01030-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T10:05:17Z","timestamp":1739441117000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01030-24"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,2,13]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2,13]]}},"alternative-id":["10.1128\/aac.01030-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.01030-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,13]]},"assertion":[{"value":"2024-07-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01030-24"}}