{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:29:40Z","timestamp":1787315380567,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cabotegravir is an integrase strand transfer inhibitor in clinical development as long\u2010acting (LA) injectable HIV preexposure prophylaxis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This phase I study assessed pharmacokinetics of cabotegravir in plasma and anatomical sites associated with sexual HIV\u20101 transmission after repeated oral and single intramuscular (IM) LA dosing in healthy adults. Following a 28\u2010day oral lead\u2010in period of cabotegravir 30\u2009mg and a washout period of 14\u201342\u2009days, participants were administered a single ultrasound\u2010guided gluteal IM cabotegravir LA 600\u2010mg injection. The study objective was to characterize cabotegravir concentrations in plasma, cervical, vaginal and rectal tissues, and cervicovaginal and rectal fluids and up to Week 12 after IM injection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nineteen participants enrolled and 16 completed the study through Week 52. Cabotegravir was detected in plasma and all tissues and fluids. Median plasma cabotegravir concentrations exceeded the in vitro protein\u2010adjusted 90% maximal inhibitory concentration through Week 12. Median tissue\u2010 and fluid\u2010to\u2010plasma cabotegravir concentration ratios across all visits were 0.32 for rectal fluid and 0.08\u20130.16 for other tissues and fluids. Adjusted\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>2<\/jats:italic>\n                      <\/jats:sup>\n                      coefficients between cabotegravir concentrations in plasma and cervical, vaginal and rectal tissues were 0.78, 0.79 and 0.90, respectively. Injection\u2010site reactions were common (88% of participants) and were mostly grade 1 in intensity (82%). Two participants reported 11 non\u2013drug\u2010related serious adverse events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Concentrations of cabotegravir in tissues and fluids were proportional to plasma over time, with strong correlations between tissue and plasma concentrations. Cabotegravir LA tissue\u2010to\u2010plasma ratios may be important for understanding its use as preexposure prophylaxis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.14980","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T01:15:40Z","timestamp":1625793340000},"page":"1667-1678","source":"Crossref","is-referenced-by-count":26,"title":["Multicompartmental pharmacokinetic evaluation of long\u2010acting cabotegravir in healthy adults for HIV preexposure prophylaxis"],"prefix":"10.1111","volume":"88","author":[{"given":"Jafar Sadik","family":"Shaik","sequence":"first","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethel D.","family":"Weld","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Edick","sequence":"additional","affiliation":[{"name":"University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Riddler","sequence":"additional","affiliation":[{"name":"University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Marzinke","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"D'Amico","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana","family":"Bakshi","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lou","sequence":"additional","affiliation":[{"name":"Precision Biosciences  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Hendrix","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelong","family":"Han","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Ford","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Margolis","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Spreen","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parul","family":"Patel","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"e_1_2_14_2_1","unstructured":"UNAIDSUNAIDS Data 2020.www.unaids.org\/en\/resources\/documents\/2020\/unaids-data. 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