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Imaging the distribution and clearance of a rectal microbicide gel and semen surrogate in the lower gastrointestinal tract
Author(s) -
Fuchs E.,
Wahl R.,
Macura K.,
Leal J.,
Grohskopf L.,
Hendrix C.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.120
Subject(s) - microbicide , medicine , rectum , semen , microbicides for sexually transmitted diseases , urology , human immunodeficiency virus (hiv) , andrology , population , immunology , environmental health , health services
Background Understanding the distribution of microbicide gel and HIV‐infected semen in the rectum is critical to safety evaluation of topical HIV microbicides, which once approved may be used rectally as well as vaginally. Methods A gel vehicle and semen surrogate were labelled with MRI contrast and 500 μCi's 99m Technetium‐sulphur colloid. Surrogate microbicide gel (10ml) was administered per rectum prior to simulated coitus; alternatively, semen surrogate (5ml) was injected through an artificial phallus following simulated coitus. Volunteers were supine for six hours and underwent both SPECT/CT and MRI immediately, 4, 10, and 24 hours after dosing. Results In all 5 studies, initial MR and SPECT/CT images showed label localized to the recto‐sigmoid with trace amounts in the rectal ampulla. Later, SPECT/CT demonstrated signal migration up to the splenic flexure. Gel migration was most rapid in the first 4 hours, though distribution continued throughout the first ten hours. Label continued to be detected 24 hours after dosing in a distribution similar to the 10 hour study. MR was less reliable in determining distribution beyond the rectum. Conclusion Using simulated coitus and surrogate gels, gel distribution was seen as far as the splenic flexure, increased with time, and persisted at least 24 hours. SPECT/CT successfully demonstrated the distribution and clearance of rectal gel and semen surrogates to facilitate safety evaluation of microbicides when used rectally. Clinical Pharmacology & Therapeutics (2005) 77 , P60–P60; doi: 10.1016/j.clpt.2004.12.120