Preclinical evaluation of UC781 microbicide vaginal drug delivery

Drug Delivery and Translational Research
Meredith R ClarkDavid R Friend

Abstract

UC781 is a potent nonnucleoside reverse transcriptase inhibitor being investigated as a potential microbicide to prevent transmission of HIV-1 both vaginally and rectally. This study was designed to investigate the in vitro drug release, in vitro permeability/safety, and in vivo pharmacokinetics in rabbits of a vaginal gel prepared with micronized or nonmicronized UC781 (UC781m and UC781nm, respectively). Gels prepared with UC781m had greater in vitro release rates (Franz cells) and permeability/tissue-associated UC781 concentrations than gels prepared with UC781nm (EpiVaginal tissues). Both gels were well tolerated under in vitro conditions compared with controls using EpiVaginal tissues. Following intravaginal administration of both gels to rabbits, tissue concentrations typically ranged from 1,000 to over 10,000 ng/g regardless of dosing regimen (single dose or 7 days once daily dosing) and sampling times (2 and 24 h post-dose). Tissue-associated concentrations were highly variable, and no statistically significant differences were found between test conditions. Plasma levels were generally low after vaginal administration: following a single dose, the concentrations were between 0.5 and 1.0 ng/mL. After 7 days repeated once...Continue Reading

References

Nov 29, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Seyoum AyehunieMitchell Klausner
Jan 15, 2008·Retrovirology·Patricia S FletcherRobin J Shattock
Oct 13, 2010·Toxicology·Seyoum AyehunieMitchell Klausner

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Citations

Mar 20, 2012·Expert Opinion on Drug Metabolism & Toxicology·Bruno SarmentoDomingos Ferreira
Sep 19, 2014·Journal of Pharmaceutical Sciences·Carolien GrammenJoachim Brouwers
Feb 24, 2012·Journal of Pharmaceutical Sciences·Patrick F KiserDavid R Friend
Oct 7, 2011·Journal of Pharmaceutical Sciences·Meredith R ClarkPatrick F Kiser
Feb 18, 2015·Advanced Drug Delivery Reviews·Rita Monteiro MachadoRita Palmeira-de-Oliveira
Mar 8, 2012·AIDS Research and Human Retroviruses·Meredith R Clark, David R Friend
Jun 1, 2011·Drug Delivery and Translational Research·Meredith R ClarkDavid R Friend
Oct 23, 2013·Molecular Diagnosis & Therapy·Lídia CunhaLuís F Metello
Jun 27, 2017·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Kashappa Goud H Desai
Jun 18, 2017·Pharmacological Reports : PR·Aleksandra AmelianKatarzyna Winnicka

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