{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:59:40Z","timestamp":1791032380815,"version":"4.1.0"},"reference-count":23,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"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":[[2013,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antiretrovirals that achieve adequate concentrations in anatomical sites of transmission are of interest for HIV prevention. A Phase I open-label pharmacokinetic (PK) study was performed to describe first dose (PK1) and steady-state (PK2) PKs of the integrase inhibitor dolutegravir (DTG) in blood plasma (BP), cervicovaginal fluid (CVF), cervical tissue (CT) and vaginal tissue (VT) in HIV type-1-negative women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 8 healthy females given DTG 50 mg daily for 5\u20137 days had 11 paired BP and CVF samples collected over 24 h following the first dose (PK1) and multiple dosing (PK2). Each woman underwent CT and VT biopsies at 1\/4 time points at PK1 and PK2 to generate composite PK profiles. DTG concentrations were analysed by validated liquid chromatography-tandem mass spectrometry methods. Non-compartmental PK analysis was performed and Spearman rank correlations determined between matrices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BP areas under the concentration\u2013time curve (AUCs) were similar to previous reports and concentrations remained greater than the protein-adjusted (PA) 90% inhibitory concentration (IC\n                      <jats:sub>90<\/jats:sub>\n                      ) for wild-type HIV (64 ng\/ml). CVF exposures were approximately 6% of BP with low inter-individual variability. CT and VT exposures were 7% of BP at PK1, and 9\u201310% of BP at PK2 with 94% of samples &gt;PA-IC\n                      <jats:sub>90<\/jats:sub>\n                      . CT and VT concentrations were correlated to each other (\u03c1=0.70, P=0.003), and to CVF at steady state (\u03c1=0.52, P=0.04). Accumulation of DTG from PK1 to PK2 occurred in BP, CT and VT, but only marginally in CVF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DTG BP PK were consistent with previously published values. CVF, CT and VT exposures were highly correlated. At PK2, DTG accumulated to a greater extent in tissue than in BP or CVF, suggesting increased tissue affinity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp2665","type":"journal-article","created":{"date-parts":[[2013,7,31]],"date-time":"2013-07-31T08:06:41Z","timestamp":1375258001000},"page":"1005-1013","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":36,"title":["Single and Multiple Dose Pharmacokinetics of Dolutegravir in the Genital Tract of HIV-Negative Women"],"prefix":"10.1177","volume":"18","author":[{"given":"Jessica L","family":"Adams","sequence":"first","affiliation":[{"name":"University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine B","family":"Patterson","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather MA","family":"Prince","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Sykes","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin N","family":"Greener","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie B","family":"Dumond","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela DM","family":"Kashuba","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Chapel Hill, NC, USA"},{"name":"University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2013,11,1]]},"reference":[{"key":"bibr1-IMP2665","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70290-0"},{"key":"bibr2-IMP2665","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61853-4"},{"key":"bibr3-IMP2665","unstructured":"Walmsley S., Antela A., Clumeck N. Dolutegravir (DTG; S\/GSK1349572) + abacavir\/lamivudine once daily statistically superior to tenofovir\/emtricitabine\/efavirenz: 48-week results \u2013SINGLE (ING114467).\n                      52nd Interscience Conference on Antimicrobial Agents and Chemotherapy\n                      , 9\u201312 September 2012, San Francisco, CA, USA. Abstract H-556b."},{"key":"bibr4-IMP2665","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis750"},{"key":"bibr5-IMP2665","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60705-2"},{"key":"bibr6-IMP2665","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32801424bd"},{"key":"bibr7-IMP2665","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283543e83"},{"key":"bibr8-IMP2665","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1105243"},{"key":"bibr9-IMP2665","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202614"},{"key":"bibr10-IMP2665","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1108524"},{"key":"bibr11-IMP2665","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110711"},{"key":"bibr12-IMP2665","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328270385a"},{"key":"bibr13-IMP2665","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32834a1dd9"},{"key":"bibr14-IMP2665","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00842-09"},{"key":"bibr15-IMP2665","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-200412150-00008"},{"key":"bibr16-IMP2665","volume-title":"Package insert","author":"Isentress (Raltegravir).","year":"2011"},{"key":"bibr17-IMP2665","unstructured":"Patterson K.B., Prince H.A., White N. Pharmacokinetics (PK) of raltegravir (RAL) in the blood plasma (BP) and genital tract (GT) in HIV+ and HIV- women.\n                      XVIII International AIDS Conference\n                      . 18\u201323 July 2010, Vienna, Austria. Poster LBPE18."},{"key":"bibr18-IMP2665","unstructured":"Jones A.E., Talameh J., Patterson K. First-dose and steady-state pharmacokinetics of raltegravir in the genital tract of HIV-negative women.\n                      10th International Workshop on Clinical Pharmacology of HIV Therapy\n                      . 15\u201317 April 2009, Amsterdam, the Netherlands. Abstract 0-06."},{"key":"bibr19-IMP2665","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01460-10"},{"key":"bibr20-IMP2665","doi-asserted-by":"publisher","DOI":"10.2165\/11584570-000000000-00000"},{"key":"bibr21-IMP2665","doi-asserted-by":"publisher","DOI":"10.1177\/096032719101000209"},{"key":"bibr22-IMP2665","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3181ae69c5"},{"key":"bibr23-IMP2665","volume-title":"Package insert","author":"Selzentry (maraviroc).","year":"2012"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP2665","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP2665","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:51:33Z","timestamp":1777380693000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP2665"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11]]},"references-count":23,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.3851\/IMP2665"],"URL":"https:\/\/doi.org\/10.3851\/imp2665","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11]]}}}