{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T15:54:40Z","timestamp":1768319680542,"version":"3.49.0"},"reference-count":75,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["104252\/Z\/14\/Z"],"award-info":[{"award-number":["104252\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            5P12-RANTES, a chemokine analogue that potently blocks the HIV CCR5 coreceptor, is being developed as both a vaginal and rectal microbicide for prevention of sexual transmission of HIV. Here, we report the first pharmacokinetic data for 5P12-RANTES following single-dose vaginal gel administration in sheep. Aqueous gel formulations containing low (1.24-mg\/ml), intermediate (6.18-mg\/ml), and high (32.0-mg\/ml; suspension-type gel) concentrations of 5P12-RANTES were assessed via rheology, syringeability, and\n            <jats:italic>in vitro<\/jats:italic>\n            release testing. Following vaginal gel administration to sheep, 5P12-RANTES concentrations were measured in vaginal fluid, vaginal tissue, and serum over a 96-h period. All gels showed non-Newtonian pseudoplastic behavior, with the high-concentration gels exhibiting a greater viscosity and cohesive structure than the intermediate- and low-concentration gels. In\n            <jats:italic>in vitro<\/jats:italic>\n            release testing, &gt;90% 5P12-RANTES was released from the low- and intermediate-concentration gels after 72 h. For the high-concentration gel, \u223c50% 5P12-RANTES was detected, attributed to protein denaturation during lyophilization and\/or subsequent solvation of the protein within the gel matrix. In sheep, 5P12-RANTES concentrations in vaginal fluid, vaginal tissue, and serum increased in a dose-dependent manner. The highest concentrations were measured in vaginal fluid (10\n            <jats:sup>5<\/jats:sup>\n            to 10\n            <jats:sup>7<\/jats:sup>\n            ng\/ml), followed by vaginal tissue (10\n            <jats:sup>4<\/jats:sup>\n            to 10\n            <jats:sup>6<\/jats:sup>\n            ng\/ml). Both of these concentration ranges are several orders of magnitude above the reported half-maximal inhibitory concentrations. The lowest concentration was measured in serum (&lt;10\n            <jats:sup>2<\/jats:sup>\n            ng\/ml). The 5P12-RANTES pharmacokinetic data are similar to those reported previously for other candidate microbicides. These data, coupled with 5P12-RANTES's potency at picomolar concentrations, its strong barrier to resistance, and the full protection that it was observed to provide in a rhesus macaque vaginal challenge model, support the continued development of 5P12-RANTES as a microbicide.\n          <\/jats:p>","DOI":"10.1128\/aac.00965-17","type":"journal-article","created":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T00:40:19Z","timestamp":1502152819000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Pharmacokinetics of the Protein Microbicide 5P12-RANTES in Sheep following Single-Dose Vaginal Gel Administration"],"prefix":"10.1128","volume":"61","author":[{"given":"John W.","family":"McBride","sequence":"first","affiliation":[{"name":"School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Dias","sequence":"additional","affiliation":[{"name":"Envigo, Huntingdon, Cambridgeshire, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Cameron","sequence":"additional","affiliation":[{"name":"Envigo, Huntingdon, Cambridgeshire, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin E.","family":"Offord","sequence":"additional","affiliation":[{"name":"Mintaka Foundation for Medical Research, Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Hartley","sequence":"additional","affiliation":[{"name":"Mintaka Foundation for Medical Research, Geneva, Switzerland"},{"name":"Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Boyd","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicky L.","family":"Kett","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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