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Tenofovir and tenofovir disoproxil fumarate pharmacokinetics from intravaginal rings

Moss, John A.a; Baum, Marc M.a; Malone, Amanda M.b; Kennedy, Seana; Kopin, Etanab; Nguyen, Calia,b; Gilman, Joshb; Butkyavichene, Irinab; Willis, Robyn A.b; Vincent, Kathleen L.c; Motamedi, Massoudc; Smith, Thomas J.a,b,d

doi: 10.1097/QAD.0b013e3283509abb
Basic Science: Concise Communications

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 (P > 0.30) 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.

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aDepartment of Chemistry, Oak Crest Institute of Science, Pasadena

bAuritec Pharmaceuticals Inc., Santa Monica, California

cCenter for Biomedical Engineering, University of Texas Medical Branch at Galveston, Galveston, Texas

dDepartment of Ophthalmology, University of Kentucky, Lexington, Kentucky, USA.

Correspondence to Marc M. Baum, 2275 E. Foothill Blvd, Pasadena, CA, USA. Tel: +1 626 817 0883; fax: +1 626 817 0884; e-mail:

Received 14 November, 2011

Revised 2 December, 2011

Accepted 20 December, 2011

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© 2012 Lippincott Williams & Wilkins, Inc.