{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:18:19Z","timestamp":1777378699696,"version":"3.51.4"},"reference-count":25,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T00:00:00Z","timestamp":1288569600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["AIDS Research and Human Retroviruses"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:p>\n                    To assess the pharmacokinetics of dapivirine in plasma and dapivirine concentrations in cervicovaginal fluids (CVF) and cervicovaginal tissues following vaginal administration of dapivirine microbicide gel in healthy, HIV-negative women for 10 days. A randomized, double-blind, phase I study was conducted at a single research center in South Africa. A total of 18 women used dapivirine gel (0.001%, 0.005%, or 0.02%) once daily on Days 1 and 10 and twice daily on Days 2\u20139. Pharmacokinetics of dapivirine were assessed in plasma on Days 1 and 10. Dapivirine concentrations were measured in CVF on Days 1 and 10 and in cervicovaginal tissues on Day 10. Safety was evaluated through laboratory tests (hematology, clinical chemistry, and urinalysis), physical examinations, and assessment of adverse events. Plasma concentrations of dapivirine increased over time with gel dose and were greater on Day 10 (C\n                    <jats:sub>max<\/jats:sub>\n                    31 to 471\u2009pg\/ml) than Day 1 (C\n                    <jats:sub>max<\/jats:sub>\n                    23 to 80\u2009pg\/ml). T\n                    <jats:sub>max<\/jats:sub>\n                    was 10\u201312\u2009h on Day 1, and 9\u2009h on Day 10. Concentrations in CVF generally increased with dose but were highly variable among participants. Mean peak values ranged from 4.6\u20138.3\u2009\u00d7\u200910\n                    <jats:sup>6<\/jats:sup>\n                    pg\/ml on Day 1 and from 2.3\u201320.7\u2009\u00d7\u200910\n                    <jats:sup>6<\/jats:sup>\n                    pg\/ml on Day 10 across dose groups. Dapivirine was detectable in all tissue biopsies on Day 10 at concentrations of 1.0\u2013356\u2009\u00d7\u200910\n                    <jats:sup>3<\/jats:sup>\n                    pg\/mg.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Dapivirine was widely distributed throughout the lower genital tract with low systemic absorption when administered in a vaginal gel formulation for 10 consecutive days. The gel was safe and well tolerated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/aid.2009.0227","type":"journal-article","created":{"date-parts":[[2010,9,21]],"date-time":"2010-09-21T07:17:43Z","timestamp":1285053463000},"page":"1181-1190","source":"Crossref","is-referenced-by-count":65,"title":["Pharmacokinetic Assessment of Dapivirine Vaginal Microbicide Gel in Healthy, HIV-Negative Women"],"prefix":"10.1177","volume":"26","author":[{"given":"Annalene M.","family":"Nel","sequence":"first","affiliation":[{"name":"International Partnership for Microbicides"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Coplan","sequence":"additional","affiliation":[{"name":"Wyeth Research"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanique C.","family":"Smythe","sequence":"additional","affiliation":[{"name":"International Partnership for Microbicides"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"McCord","sequence":"additional","affiliation":[{"name":"International Partnership for Microbicides"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Mitchnick","sequence":"additional","affiliation":[{"name":"Particle Sciences, Inc."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulina E.","family":"Kaptur","sequence":"additional","affiliation":[{"name":"International Partnership for Microbicides"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Romano","sequence":"additional","affiliation":[{"name":"International Partnership for Microbicides"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2010,11,1]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"Report on the global HIV\/AIDS epidemic 2008: executive summary July 2008UNAIDS\/08.27E\/JC1511E. ISBN 978 92 9 173717 8http:\/\/www.unaids.org\/en\/KnowledgeCentre\/HIVData\/GlobalReport\/2008\/2008_Global_report.asp."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.qai.0000243056.59860.c1"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/154099903322404302"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32832c413d"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2007.04.015"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000194797.59046.8f"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.94.7.1159"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612043386374"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00330-07"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31802bb35f"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2006.06.026"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki326"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0b013e328305b96e"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.1.337-339.2004"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01156-08"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200307250-00003"},{"key":"e_1_3_3_18_2","unstructured":"The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0 December 2004. http:\/\/www.ucdmc.ucdavis.edu\/clinicaltrials\/documents\/DAIDS_AE_GradingTable_FinalDec2004.pdf."},{"key":"e_1_3_3_19_2","doi-asserted-by":"crossref","unstructured":"Nel A Smythe SC Habibi S Romano J. Pharmacokinetics of two dapivirine vaginal microbicide gels their safety vs. hydroxyethyl cellulose-based universal placebo gel. J Acquir Immune Defic Syndr 2010 Jun 22[Epub ahead of print].","DOI":"10.1097\/QAI.0b013e3181e3293a"},{"key":"e_1_3_3_20_2","unstructured":"Van \u2019t Klooster G van der Geest R Gill\u00e9 D. Pharmacokinetics tolerability and safety of multiple oral doses of TMC120 (R147681) in 32 healthy subjectsTibotec Pharmaceuticals Ltd. Trial No. TIBO-0001-104 Report No. TMC120-C104-CRRApril 9 2004."},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000210608.70762.c3"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025974"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2008.02687.x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2006.05.013"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2009.07.005"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2009.07.012"}],"container-title":["AIDS Research and Human Retroviruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/aid.2009.0227","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/aid.2009.0227","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/aid.2009.0227","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:12:00Z","timestamp":1777367520000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/aid.2009.0227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11]]},"references-count":25,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2010,11]]}},"alternative-id":["10.1089\/aid.2009.0227"],"URL":"https:\/\/doi.org\/10.1089\/aid.2009.0227","relation":{},"ISSN":["0889-2229","1931-8405"],"issn-type":[{"value":"0889-2229","type":"print"},{"value":"1931-8405","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11]]}}}