title: Quantitative assessment of altered rectal mucosal permeability due to rectally applied nonoxynol-9, biopsy, and simulated intercourse.
abstract: BACKGROUND
  Microbicide toxicity may reduce the efficacy of topical preexposure prophylaxis for human immunodeficiency virus (HIV) transmission. Noninvasive quantitative measures of microbicide toxicity would usefully inform microbicide development.
  
  
  METHODS
  Ten subjects received 3 one-time interventions: 5 mL of Normosol-R fluid alone (negative control), 5 mL of 2% nonoxynol-9 (N-9) gel, and 5 mL of Normosol-R with coital simulation and sigmoidoscopic biopsy (CS + BX). Each dose of N-9 and Normosol-R contained 500 µCi of (99m)technetium-diethylene triamine pentaacetic acid. Plasma and urine radioactivity was assessed over 24 hours.
  
  
  RESULTS
  The plasma radioisotope concentration peaked 1 hour after N-9 dosing. The mean maximum radioisotope concentration after N-9 receipt was 12.0 times (95% confidence interval [CI], 6.8-21.0) and 8.4 times (95% CI, 5.2-13.5) the mean concentration after Normosol-R control receipt and CS + BX receipt, respectively; paired differences persisted for 24 hours. After N-9 dosing, the urine isotope level was 3.6 times (95% CI, 1.1-11.4) the level observed 8 hours after Normosol-R control receipt and 4.0 times (95% CI, 1.4-11.4) the level observed 4 hours after CS + BX receipt. Permeability after CS + BX receipt was greater than that after Normosol-R control receipt in 0-2-hour urine specimens only (mean permeability, 2.4; 95% CI, 1.0-5.8) but was not greater in blood.
  
  
  CONCLUSIONS
  Plasma sampling after rectal radioisotope administration provided quantitative estimates of altered mucosal permeability after chemical and mechanical stresses. Permeability testing may provide a useful noninvasive adjunct to assess the mucosal effects of candidate microbicides. Clinical Trials Registration. NCT00389311.
authors: Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-5554, USA. ejfuchs@jhmi.edu
authors: Edward J
authors: EJ
authors: Fuchs
authors: Lisa A
authors: LA
authors: Grohskopf
authors: Linda A
authors: LA
authors: Lee
authors: Rahul P
authors: RP
authors: Bakshi
authors: Craig W
authors: CW
authors: Hendrix
mesh_terms: D001706:Biopsy / Q000009:adverse effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000503:physiopathology; D017137:Nonoxynol / Q000009:adverse effects*; D010539:Permeability / Q000187:drug effects*; D010949:Plasma / Q000737:chemistry; D011868:Radioisotopes / Q000008:administration & dosage / Q000097:blood; D012007:Rectum / Q000187:drug effects* / Q000503:physiopathology; D013089:Spermatocidal Agents / Q000009:adverse effects*; D013667:Technetium / Q000008:administration & dosage / Q000097:blood
chemical_list: D011868:Radioisotopes; D013089:Spermatocidal Agents; D017137:Nonoxynol; D013667:Technetium