Macaques given an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) gel called UC781 in repeated
vaginal and rectal applications exhibited no evidence of systemic
absorption, researchers report.
Dr. D. L. Patton of the University of Washington in Seattle and
colleagues administered rectal and vaginal applications of two
different concentrations of UC781, 1.0% and 0.1%, to pig-tailed
macaques. Results of their study are published in the May issue of
Antimicrobial Agents and Chemotherapy.
Using liquid chromatography, the investigators saw no systemic
absorption on repeated applications of either formulation of the
microbicide. However, UC781 was detectable on cervicovaginal lavage up
to six hours after application.
Vaginal applications of UC781 appeared safe on colposcopy and in assessments of vaginal cytokine levels and microflora.
In contrast, rectal applications of the 1.0% formulation were
accompanied by increases in a number of cytokines. Application of the
0.1% concentration was not. "The clinical significance of this finding
remains unknown," Dr. Patton told Reuters Health.
"UC781 may be localizing in some as yet unidentified cellular
compartment," the Seattle investigator acknowledged. "It is possible
that any UC781 that may have been absorbed into the systemic
circulation, may have localized in the blood cells, and thus would not
have been detected in our analytical analyses. We are currently
developing an analytical method appropriate for detection of UC781 in
blood cells in order to explore this possibility."
The researchers say their findings support continued research with UC781 as a topical anti-HIV microbicide.
"A new research grant through the U19 Co-Operative agreement funding
mechanism sponsored by the NIH is currently under peer review.
Continued grant support would allow our research team to further
explore the feasibility of UC781 as a topical microbicide," Dr. Patton
Antimicrob Agents Chemother 2007;51:1608-1615.
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