{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:36:57Z","timestamp":1791423417130,"version":"4.3.3"},"reference-count":6,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2015,5]]},"abstract":"\n Background<\/jats:title>\n Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). Doravirine has low potential to cause drug\u2013drug interactions since it is primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The pharmacokinetics and safety of doravirine were investigated in two double-blind, dose-escalation studies in healthy males. Thirty-two subjects received single doses of doravirine (6\u20131,200 mg) or matching placebo tablets; 40 subjects received doravirine (30\u2013750 mg) or matching placebo tablets once daily for 10 days. In addition, the effect of doravirine (120 mg for 14 days) on single-dose pharmacokinetics of the CYP3A substrate midazolam was evaluated (10 subjects).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The maximum plasma concentration (C\n max<\/jats:sub>\n ) of doravirine was achieved within 1\u20135 h with an apparent terminal half-life of 12\u201321 h. Consistent with single-dose pharma-cokinetics, steady state was achieved after approximately 7 days of once daily administration, with accumulation ratios (day 10\/day 1) of 1.1\u20131.5 in the area under the plasma concentration\u2013time curve during the dosing interval (AUC\n 0\u201324<\/jats:sub>\n h<\/jats:sub>\n ), C\n max<\/jats:sub>\n and trough plasma concentration (C\n 24<\/jats:sub>\n h<\/jats:sub>\n ). All dose levels produced C\n 24<\/jats:sub>\n h<\/jats:sub>\n >19 nM. Administration of 50 mg doravirine with a high-fat meal was associated with slight elevations in AUC time zero to infinity (AUC\n 0\u2013\u221e<\/jats:sub>\n ) and C\n 24<\/jats:sub>\n h<\/jats:sub>\n with no change in C\n max<\/jats:sub>\n . Midazolam AUC\n 0\u2013\u221e<\/jats:sub>\n was slightly reduced by coadministration of doravirine (geometric mean ratio 0.82, 90% CI 0.70, 0.97). There was no apparent relationship between adverse event frequency or intensity and doravirine dose. No rash or significant central nervous system events other than headache were reported.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once-daily dosing. Doravirine at steady state slightly reduced the exposure of coadministered midazolam, to a clinically unimportant extent.<\/jats:p>\n <\/jats:sec>","DOI":"10.3851\/imp2920","type":"journal-article","created":{"date-parts":[[2014,12,3]],"date-time":"2014-12-03T10:18:56Z","timestamp":1417601936000},"page":"397-405","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":75,"title":["Safety, Tolerability and Pharmacokinetics of Doravirine, a Novel HIV Non-Nucleoside Reverse Transcriptase Inhibitor, after Single and Multiple doses in Healthy Subjects"],"prefix":"10.1177","volume":"20","author":[{"given":"Matt S","family":"Anderson","sequence":"first","affiliation":[{"name":"Merck & Co., Inc., Kenilworth, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"Gilmartin","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc., Kenilworth, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Cilissen","sequence":"additional","affiliation":[{"name":"Merck, Sharp & Dohme (Europe) Inc., Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"De Lepeleire","sequence":"additional","affiliation":[{"name":"Merck, Sharp & Dohme (Europe) Inc., Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Van Bortel","sequence":"additional","affiliation":[{"name":"University Hospital Ghent, Drug Research Unit, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa F","family":"Dockendorf","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc., Kenilworth, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernestina","family":"Tetteh","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc., Kenilworth, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June K","family":"Ancona","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc., Kenilworth, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Liu","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc., Kenilworth, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Guo","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc., Kenilworth, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A","family":"Wagner","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc., Kenilworth, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan R","family":"Butterton","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc., Kenilworth, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,5,1]]},"reference":[{"key":"bibr1-IMP2920","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2009.09.008"},{"key":"bibr2-IMP2920","unstructured":"Lai M.T. Antiviral activity and\n in vitro\n mutation development pathways of MK-1439: a novel non-nucleoside reverse transcriptase inhibitor (NNRTI).\n Interscience Conference\n on Antimicrobial Agents & Chemotherapy (ICAAC).\n 9\u201312 September 2012, San Francisco, CA, USA. Abstract H551."},{"key":"bibr3-IMP2920","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.9.4096"},{"key":"bibr4-IMP2920","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.6.1386"},{"key":"bibr5-IMP2920","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.3.913-916.2002"},{"key":"bibr6-IMP2920","unstructured":"Morales-Ramirez J.O., Gatell J.M., Hagins D.P. Safety & antiviral effect of MK-1439, a novel NNRTI, (+TDF\/ FTC) in ART-naive HIV infected patients.\n Conference on Retroviruses and Opportunistic Infections (CROI).\n 3\u20136 March 2014, Boston, MA, USA. Abstract 92LB."}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP2920","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP2920","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:52:12Z","timestamp":1777380732000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP2920"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,1]]},"references-count":6,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.3851\/IMP2920"],"URL":"https:\/\/doi.org\/10.3851\/imp2920","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,1]]}}}