{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:04:50Z","timestamp":1778126690526,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,4,17]],"date-time":"2017-04-17T00:00:00Z","timestamp":1492387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A new once\u2010daily formulation of raltegravir, an integrase strand transfer inhibitor indicated in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus\u20131 infection, is under development. Single\u2010dose and steady\u2010state pharmacokinetics of 1200 mg for 2 formulations of raltegravir were characterized in 2 open\u2010label phase 1 studies in healthy male and female subjects aged 18 to 55 years. The new raltegravir 600\u2010mg formulation had a higher relative bioavailability compared with the 400\u2010mg tablets. Once absorbed, both 3 \u00d7 400\u2010mg and 2 \u00d7 600\u2010mg dosage forms of raltegravir exhibited similar systemic pharmacokinetics; in dictating bioavailability, differences were from increased absorption that was the result of improved in vivo disintegration\/dissolution. Food had a smaller effect on the pharmacokinetics of raltegravir when given as 2 \u00d7 600\u2010mg formulation (42% vs 73% decrease in AUC<jats:sub>0\u2013last<\/jats:sub>). Steady state was generally reached in 2 days, with little to no accumulation with multiple\u2010dose administration. Raltegravir 1200 mg was found to exhibit pharmacokinetic properties amenable for once\u2010daily dosing and was generally well tolerated in healthy subjects after single and multiple doses. The new formulation improved the bioavailability of this Biopharmaceutics Classification System class II compound.<\/jats:p>","DOI":"10.1002\/cpdd.358","type":"journal-article","created":{"date-parts":[[2017,4,17]],"date-time":"2017-04-17T15:58:41Z","timestamp":1492444721000},"page":"196-206","source":"Crossref","is-referenced-by-count":25,"title":["Single\u2010 and Multiple\u2010Dose Pharmacokinetics of Once\u2010Daily Formulations of Raltegravir"],"prefix":"10.1002","volume":"7","author":[{"given":"Rajesh","family":"Krishna","sequence":"first","affiliation":[{"name":"Merck Research Laboratories Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew L.","family":"Rizk","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Larson","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"Schulz","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippos","family":"Kesisoglou","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radu","family":"Pop","sequence":"additional","affiliation":[{"name":"Pharma Medica Research Inc.  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,4,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010387428"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100281"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010367652"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007310382"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/588794"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01543-07"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01468-08"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12632"},{"issue":"2","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3851\/IMP2993","article-title":"A pharmacokinetic drug drug interaction study between raltegravir and citalopram","volume":"21","author":"Blonk MI","year":"2016","journal-title":"Antivir Ther"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00157-11"},{"issue":"1","key":"e_1_2_9_12_1","first-page":"A27","article-title":"HIV integrase inhibitor dissociation rates correlate with efficacy in vitro","volume":"14","author":"Grobler JA","year":"2009","journal-title":"Antivir Ther."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70196-7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.06417-11"},{"key":"e_1_2_9_15_1","unstructured":"WenningLA RizkML TaylorA StoneJ PolandB.A viral dynamics model describes monotherapy and combination data with raltegravir including differences between BID and QD dosing in QDMRK study. Presentation at the 14th International Workshop on Clinical Pharmacology of HIV Therapy Amsterdam The Netherlands;2013."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/2168479016657130"},{"key":"e_1_2_9_17_1","unstructured":"KrishnaR RizkML SchulzV IngelseB LarsonP.A single dose food effect study of raltegravir formulations [abstract PE10\/17]. 14th European AIDS Conference October 16\u201019th 2013 Brussels."},{"issue":"2","key":"e_1_2_9_18_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/cmdc.201402393","article-title":"Discovery of MK\u20108970: an acetal carbonate prodrug of raltegravir with enhanced colonic absorption","volume":"10","author":"Walji AM","year":"2015","journal-title":"Chem Med Chem"},{"issue":"1","key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jchromb.2007.06.032","article-title":"Determination of the HIV integrase inhibitor, MK\u20100518 (raltegravir), in human plasma using 96\u2010well liquid\u2010liquid extraction and HPLC\u2010MS\/MS","volume":"857","author":"Merschman SA","year":"2007","journal-title":"J Chromatogr B Ananlyt Technol Biomed Life Sci"},{"key":"e_1_2_9_20_1","volume-title":"Pharmacokinetics","author":"Gibaldi M","year":"1975"},{"key":"e_1_2_9_21_1","unstructured":"Food\u2010Effect Bioavailability and Fed Bioequivalence Studies.U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER)December 2002."},{"key":"e_1_2_9_22_1","unstructured":"CahnP KaplanR SaxP et\u00a0al.Raltegravir (RAL) 1200\u00a0mg once daily (QD) is non\u2010inferior to RAL 400 mg twice daily (BID) in combination with tenofovir\/emtricitabine in treatment\u2010na\u00efve HIV\u20101 infected subjects: Week 48 results. 21st International AIDS Conference 2016 Durban South Africa Abstract FRAB01013LB."},{"issue":"12","key":"e_1_2_9_23_1","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.1128\/AAC.00942-12","article-title":"Comparison of the in vivo pharmacokinetics and in vitro dissolution of raltegravir in HIVpatients receiving the drug by swallowing or by chewing","volume":"56","author":"Cattaneo D","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1086\/596503"},{"key":"e_1_2_9_25_1","unstructured":"RizkML KrishnaR SchulzV Bruggencate\u2010Broeders tenJ LarsonP WenningL.A multiple dose study of raltegravir formulations. Conference on Retroviruses and Opportunistic Infections (CROI) Boston MA 2014."},{"issue":"5","key":"e_1_2_9_26_1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/COH.0b013e3283562a27","article-title":"The use of HIV\u20101 integrase inhibitors in antiretroviral naive patients","volume":"7","author":"Lennox JL.","year":"2012","journal-title":"Curr Opin HIV AIDS"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpdd.358","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T15:17:09Z","timestamp":1695914229000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,17]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1002\/cpdd.358"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.358","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,17]]}}}