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Formulation, pharmacokinetics and pharmacodynamics of topical microbicides.

Abstract
The development of safe topical microbicides that effectively prevent human immunodeficiency virus (HIV) infection is a major goal in curbing the human immunodeficiency virus pandemic. A number of past failures resulting from mucosal toxicity or lack of efficacy have informed the field. Products that caused toxicity to the female genital tract mucosa, and thereby increased the likelihood of HIV acquisition, included nonoxynol 9, cellulose sulfate, and C31 G vaginal gel Savvy. Topical products that were ineffective in preventing HIV infection include BufferGel, Carraguard, and PRO 2000. Antiretroviral drugs such as tenofovir and dapivirine formulated into microbicide products have shown promise, but there is much to learn about ideal product formulation and acceptability, and drug distribution and disposition (pharmacokinetics). Current formulations for water-soluble molecules include vaginally or rectally applied gels, vaginal rings, films and tablets. Dosing strategies (e.g. coitally dependent or independent) will be based on the pharmacokinetics of the active ingredient and the tolerance for less than perfect adherence.
AuthorsJessica L Adams, Angela D M Kashuba
JournalBest practice & research. Clinical obstetrics & gynaecology (Best Pract Res Clin Obstet Gynaecol) Vol. 26 Issue 4 Pg. 451-62 (Aug 2012) ISSN: 1532-1932 [Electronic] Netherlands
PMID22306523 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
CopyrightCopyright © 2012 Elsevier Ltd. All rights reserved.
Chemical References
  • Anti-HIV Agents
  • Anti-Infective Agents, Local
  • Organophosphonates
  • Vaginal Creams, Foams, and Jellies
  • Tenofovir
  • Adenine
Topics
  • Adenine (analogs & derivatives, chemistry, pharmacokinetics, pharmacology)
  • Animals
  • Anti-HIV Agents (administration & dosage, pharmacokinetics)
  • Anti-Infective Agents, Local (chemistry, pharmacokinetics, pharmacology)
  • Female
  • HIV
  • HIV Infections (prevention & control)
  • Humans
  • Mice
  • Organophosphonates (chemistry, pharmacokinetics, pharmacology)
  • Tenofovir
  • Treatment Outcome
  • Vaginal Creams, Foams, and Jellies (administration & dosage, pharmacokinetics)

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