{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:43:27Z","timestamp":1775151807901,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,11,13]],"date-time":"2012-11-13T00:00:00Z","timestamp":1352764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Rectally applied drugs have been imaged using radioisotopes and magnetic resonance contrast agents. However, prior studies have not described the distribution and clearance of rectally\u2010applied drugs in quantitative terms with respect to complex three dimensional paths through the gastrointestinal tract. Such tools would allow statistical comparisons of candidate products in development or comparison of drug product with the distribution of a drug target, for example, HIV infected seminal fluid.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003New quantitative spatial parameters, derived from three dimensional curve fitting, have been successfully applied in this study to quantify the distribution of rectally\u2010applied gels. Indirect assessment using nuclear medicine techniques avoided the distortion and redistribution associated with sigmoidoscopic sampling. Thus, these measurements can be repeated over time to create concentration\u2013distance\u2013time surfaces to describe rectal product distribution and clearance within the gastrointestinal lumen to inform microbicide and other rectal product development.<\/jats:p><jats:p><jats:bold>AIMS<\/jats:bold> We sought to describe quantitatively the distribution of rectally administered gels and seminal fluid surrogates using novel concentration\u2013distance parameters that could be repeated over time. These methods are needed to develop rationally rectal microbicides to target and prevent HIV infection.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold> Eight subjects were dosed rectally with radiolabelled and gadolinium\u2010labelled gels to simulate microbicide gel and seminal fluid. Rectal doses were given with and without simulated receptive anal intercourse. Twenty\u2010four hour distribution was assessed with indirect single photon emission computed tomography (SPECT)\/computed tomography (CT) and magnetic resonance imaging (MRI), and direct assessment via sigmoidoscopic brushes. Concentration\u2013distance curves were generated using an algorithm for fitting SPECT data in three dimensions. Three novel concentration\u2013distance parameters were defined to describe quantitatively the distribution of radiolabels: maximal distance (D<jats:sub>max<\/jats:sub>), distance at maximal concentration (D<jats:sub><jats:italic>C<\/jats:italic>max<\/jats:sub>) and mean residence distance (D<jats:sub>ave<\/jats:sub>).<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold> The SPECT\/CT distribution of microbicide and semen surrogates was similar. Between 1\u2003h and 24\u2003h post dose, the surrogates migrated retrograde in all three parameters (relative to coccygeal level; geometric mean [95% confidence interval]): maximal distance (D<jats:sub>max<\/jats:sub>), 10\u2003cm (8.6\u201312) to 18\u2003cm (13\u201326), distance at maximal concentration (D<jats:sub><jats:italic>C<\/jats:italic>max<\/jats:sub>), 3.8\u2003cm (2.7\u20135.3) to 4.2\u2003cm (2.8\u20136.3) and mean residence distance (D<jats:sub>ave<\/jats:sub>), 4.3\u2003cm (3.5\u20135.1) to 7.6\u2003cm (5.3\u201311). Sigmoidoscopy and MRI correlated only roughly with SPECT\/CT.<\/jats:p><jats:p><jats:bold>CONCLUSIONS<\/jats:bold> Rectal microbicide surrogates migrated retrograde during the 24\u2003h following dosing. Spatial kinetic parameters estimated using three dimensional curve fitting of distribution data should prove useful for evaluating rectal formulations of drugs for HIV prevention and other indications.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2012.04267.x","type":"journal-article","created":{"date-parts":[[2012,3,9]],"date-time":"2012-03-09T06:50:30Z","timestamp":1331275830000},"page":"1013-1022","source":"Crossref","is-referenced-by-count":19,"title":["Quantification of the spatial distribution of rectally applied surrogates for microbicide and semen in colon with SPECT and magnetic resonance imaging"],"prefix":"10.1111","volume":"74","author":[{"given":"Ying J.","family":"Cao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian S.","family":"Caffo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward J.","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda A.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liye","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahul P.","family":"Bakshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Macura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wasif A.","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard L.","family":"Wahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa A.","family":"Grohskopf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig W.","family":"Hendrix","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,11,13]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193748"},{"key":"e_1_2_7_3_2","unstructured":"MTN Statement on Decision to Discontinue Use of Tenofovir Gel in VOICE a Major HIV Prevention Study in Women. 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