Rectal applications of nonoxynol-9 cause tissue disruption in a monkey model.
BACKGROUND
Efforts to develop topical microbicide products have all but ignored evaluation for rectal use.


OBJECTIVE
The goal of this study was to assess the effects of multiple rectal applications of Conceptrol (containing 4% nonoxynol-9) on flora and mucosal tissues in the pig-tailed macaque model.


METHODS
Monkeys (8 per group) received daily rectal applications of Conceptrol, placebo gel, or no product, for 3 days. At each visit, a preapplication rectal lavage specimen and swab specimen for microbiology and pH determination were collected. Conceptrol or placebo gel (2.5 ml) was then administered intrarectally. Fifteen minutes after application, samples were again collected.


RESULTS
Gross observation of rectal lavage indicated sheets of epithelium 15 minutes after application of the nonoxynol-9 product. Histopathology of these samples revealed epithelial sheets with stroma attached. The presence of H(2)O(2)-producing lactobacilli remained relatively constant, whereas that of H(2)O(2)-producing viridans streptococci diminished in all nonoxynol-9-exposed animals in which these organisms were detected at baseline.


CONCLUSIONS
Repeated applications of nonoxynol-9 disrupts the rectal mucosa of the pig-tailed macaque. The disruption of these tissues could have serious implications for an increase in likelihood of acquisition of sexually transmitted infection/HIV in humans.
Patton
Dorothy L
DL
Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington 98195-6460, USA. dpatton@u.washington.edu
Cosgrove Sweeney
Yvonne T
YT
Rabe
Lorna K
LK
Hillier
Sharon L
SL
D000285:Administration, Rectal; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects* / Q000473:pathology; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008254:Macaca nemestrina; D023421:Models, Animal; D009092:Mucous Membrane / Q000187:drug effects* / Q000473:pathology; D017137:Nonoxynol / Q000494:pharmacology*; D012007:Rectum / Q000187:drug effects* / Q000473:pathology; D013501:Surface-Active Agents / Q000494:pharmacology*
D000891:Anti-Infective Agents, Local; D013501:Surface-Active Agents; D017137:Nonoxynol