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

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 47; no. 3; pp. 329 - 333
• Main Authors: Vourvahis, Manoli, Tappouni, Hiba L, Patterson, Kristine B, Chen, Ya-Chi, Rezk, Naser L, Fiscus, Susan A, Kearney, Brian P, Rooney, James F, Hui, James, Cohen, Myron S, Kashuba, Angela D M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-03-2008; Lippincott Williams & Wilkins; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Adenine - analogs & derivatives; Adenine - blood; Adenine - pharmacokinetics; Adenine - therapeutic use; Adult; AIDS/HIV; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Biological and medical sciences; Blood tests; Chromatography, High Pressure Liquid; Drug therapy; Fundamental and applied biological sciences. Psychology; Genitalia, Male - drug effects; Genitalia, Male - metabolism; Genitalia, Male - virology; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Organophosphonates - blood; Organophosphonates - pharmacokinetics; Organophosphonates - therapeutic use; Pharmacology; Reproductive system; Ribonucleic acid; RNA; RNA, Viral - blood; RNA, Viral - genetics; Spectrophotometry, Ultraviolet; Studies; Tandem Mass Spectrometry; Tenofovir; Viral diseases; Virology; genital tract; Microbiology; sexual transmission; antiretroviral therapy; Retroviridae; Lentivirus; Virology; Infection; Virus; Tenofovir; Chemotherapy; Treatment; Sexually transmitted disease; HIV; pharmacokinetics; Antiviral; Human immunodeficiency virus
• ISSN: 1525-4135; 1944-7884
• DOI: 10.1097/QAI.0b013e3181632cc3

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.