Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
AIDS. 2012 Mar 27;26(6):707-10. doi: 10.1097/QAD.0b013e3283509abb.

Tenofovir and tenofovir disoproxil fumarate pharmacokinetics from intravaginal rings.

Author information

  • 1Department of Chemistry, Oak Crest Institute of Science, Pasadena CA, USA.

Abstract

OBJECTIVES:

To compare the distribution of tenofovir in sheep vaginal lumen, tissue, and plasma following topical delivery of the antiretroviral drug from intravaginal rings, either as tenofovir or the disoproxil fumarate prodrug.

DESIGN:

Comparative pharmacokinetic study in sheep.

METHOD:

Intravaginal rings formulated to achieve equivalent release rates of tenofovir and its disoproxil fumarate prodrug were evaluated for 28 days in sheep, with four animals in each group. Drug concentrations were measured by high-performance liquid chromatography-mass spectrometry.

RESULTS:

Tenofovir levels in cervicovaginal lavage were indistinguishable (Pā€Š>ā€Š0.30) in both groups, but tissue levels in animals receiving the prodrug were 86-fold higher than those receiving tenofovir, and approximately 50 times higher than the level shown to be protective of HIV infection in the CAPRISA 004 trial.

CONCLUSION:

This is the first study to compare the pharmacokinetics of tenofovir and its disoproxil fumarate prodrug administered topically to the vaginal tract. These in-vivo data show that the prodrug leads to significantly higher drug tissue levels than tenofovir, a finding that may have important implications for the development of preexposure prophylaxis strategies based on topical delivery of antivirals to the female genital tract.

PMID:
22210639
[PubMed - indexed for MEDLINE]
PMCID:
PMC3855348
Free PMC Article

Images from this publication.See all images (2)Free text

Fig. 1
Fig. 2
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Lippincott Williams & Wilkins Icon for PubMed Central
    Loading ...
    Write to the Help Desk