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The Pharmacokinetics and Viral Activity of Tenofovir in the Male Genital Tract

Vourvahis, Manoli PharmD*; Tappouni, Hiba L PharmD*; Patterson, Kristine B MD; Chen, Ya-Chi PharmD*; Rezk, Naser L PhD*; Fiscus, Susan A PhD; Kearney, Brian P PharmD§; Rooney, James F MD§; Hui, James PhD; Cohen, Myron S MD; Kashuba, Angela D M BScPhm, PharmD, DABCP*

JAIDS Journal of Acquired Immune Deficiency Syndromes: March 1st, 2008 - Volume 47 - Issue 3 - p 329-333
doi: 10.1097/QAI.0b013e3181632cc3
Clinical Science

Objective: To measure tenofovir (TFV) concentrations in the male genital tract (GT) after single and multiple doses of tenofovir disoproxil fumarate (TDF) and evaluate the HIV-1 RNA response to monotherapy.

Design and Methods: A pharmacokinetic study of blood plasma (BP) and GT TFV concentrations in 9 men was conducted after 1 and ≥14 doses of TDF. TFV concentrations were measured by validated high-performance liquid chromatography-ultraviolet or tandem mass spectrometry methods, and HIV-1 RNA was measured using Roche (Roche Molecular Systems, Branchburg, NJ) or bioMerieux (bioMerieux, Durham, NC) kits.

Results: TFV GT concentrations were 4.4-fold ± 5.1-fold higher than BP after dose 1 and 5.1-fold ± 6.8-fold higher than BP after dose 14. Intracellular GT TFV-diphosphate concentrations were 9.4-fold higher than BP after dose 1 and 17.5-fold ± 22.6-fold higher after dose 7. After 14 days of TDF monotherapy, HIV-1 RNA decreased by 0.9 log10 copies/mL in blood and 1.0 log10 copies/mL in the GT.

Conclusions: High TFV concentrations were achieved rapidly in the GT of all subjects after single and multiple doses and potently reduced BP and GT HIV-1 RNA levels.

From the *Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina, Chapel Hill, NC; †Department of Medicine, University of North Carolina, Chapel Hill, NC; ‡Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC; §Gilead Sciences, Inc., Foster City, CA; and ∥Gilead Sciences, Inc., Durham, NC.

Received for publication March 30, 2007; accepted November 26, 2007.

Supported in part by Gilead Sciences, Inc., the National Institute of Allergy and Infectious Diseases (NIAID) (grant AI54980 to A. D. M. Kashuba), the UNC Center for AIDS Research/NIAID (grant P30 AI50410 to A. D. M. Kashuba, N. L. Rezk and S. A. Fiscus), the UNC General Clinical Research Center/National Institutes of Health (grant RR00046), and the UNC Building Interdisciplinary Research Careers in Women's Health program (grant HD001441 to K. B. Patterson).

This research was presented in part at the 13th Conference on Retroviruses and Opportunistic Infections, Denver, CO, February 5-8, 2006.

Drs. Kearney, Rooney, and Hui are employed by Gilead Sciences. The remaining authors do not have conflicts of interest related to this research or manuscript.

Correspondence to: Angela D. M. Kashuba, BScPharm, PharmD, DABCP, Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina at Chapel Hill, 3318 Kerr Hall, CB 7360, Chapel Hill, NC 27599-7360 (e-mail: akashuba@unc.edu).

© 2008 Lippincott Williams & Wilkins, Inc.