title: Direct measurement of in-vivo vaginal microbicide levels of PRO 2000 achieved in a human safety study.
abstract: OBJECTIVE
  To directly measure the cervico-vaginal lavage (CVL) and plasma PRO 2000 concentrations achieved by vaginal dosing.
  
  
  METHODS
  A sub-study of a prospective randomized, double-blind phase 1 trial of a candidate vaginal microbicide, PRO 2000 gel.
  
  
  METHODS
  Thirty-six sexually abstinent women self-administered 4% PRO 2000 gel, 0.5% PRO 2000 gel or placebo gel twice on day 0 and then once daily for a further 12 days.
  
  
  RESULTS
  There was no evidence of systemic absorption of PRO 2000. PRO 2000 concentrations in CVL exceeded 25 microg/ml in all women in both the 4 and 0.5% groups at 2 h post-first dose, and in 10 of 12 of the women in the 4% gel group compared with five of 12 of women in the 0.5% group at 12 h post-seventh dose. Single use of both 4 and 0.5% PRO 2000 gels was therefore associated with levels of PRO 2000 in CVL that would be capable of preventing HIV infection in vitro, although the 4% gel gave a greater margin of excess. Levels substantially in excess of the target concentration were present 12 h after repeated dosing in twice as many 4% gel recipients compared with 0.5% gel recipients.
  
  
  CONCLUSIONS
  Both PRO 2000 gel strengths provided satisfactory in-vivo HIV inhibitory concentrations. However, our observations show that higher concentrations of PRO 2000 are likely to provide a greater margin of potential efficacy in the context of sexual intercourse provided safety issues are equivalent for differing concentrations of the agent.
authors.affiliation: Hull York Medical School, University of York, Heslington, York, UK. charles.lacey@hyms.ac.uk
authors.forename: Charles J N
authors.initials: CJ
authors.lastname: Lacey
authors.forename: Anne
authors.initials: A
authors.lastname: Wright
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Weber
authors.forename: Albert T
authors.initials: AT
authors.lastname: Profy
mesh_terms: D000042:Absorption; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005782:Gels / Q000008:administration & dosage; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D009282:Naphthalenesulfonates / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D011108:Polymers / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D011446:Prospective Studies; D012646:Self Administration; D014621:Vagina / Q000737:chemistry*; D044364:Vaginal Douching / Q000379:methods
chemical_list: D019380:Anti-HIV Agents; D005782:Gels; D009282:Naphthalenesulfonates; C120231:PRO 2000; D011108:Polymers