{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:39:41Z","timestamp":1775151581741,"version":"3.50.1"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            . Both inhibitors were released continuously during 28 days from rings\n            <jats:italic>in vitro<\/jats:italic>\n            at rates of 100 to 2,500 \u03bcg\/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were \u223c10\n            <jats:sup>6<\/jats:sup>\n            -fold greater than the 50% inhibitory concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes\n            <jats:italic>in vitro<\/jats:italic>\n            . Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle.\n          <\/jats:p>","DOI":"10.1128\/aac.05810-11","type":"journal-article","created":{"date-parts":[[2012,2,14]],"date-time":"2012-02-14T04:11:22Z","timestamp":1329192682000},"page":"2251-2258","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":52,"title":["Sustained Release of the CCR5 Inhibitors CMPD167 and Maraviroc from Vaginal Rings in Rhesus Macaques"],"prefix":"10.1128","volume":"56","author":[{"given":"R. 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Delay of simian human immunodeficiency virus infection and control of viral replication in vaccinated macaques challenged in the presence of a topical microbicide. AIDS 25:1833\u20131841.","journal-title":"AIDS"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1105243"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/499163"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/313818"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1319"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1093\/oxfordjournals.humrep.a136677","article-title":"The temporal relationship between vaginal fluid volumes obtained with the Rovumeter vaginal aspirator and the fertile phase of the cycle","volume":"3","author":"Flynn AM","year":"1988","unstructured":"FlynnAM McCarthyAM DockerM RoystonJP. 1988. 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