The pharmacokinetics and viral activity of tenofovir in the male genital tract.
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.


METHODS
A pharmacokinetic study of blood plasma (BP) and GT TFV concentrations in 9 men was conducted after 1 and > or =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 ofTDF 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.
Vourvahis
Manoli
M
Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina, Chapel Hill , NC 27599-7360, USA.
Tappouni
Hiba L
HL
Patterson
Kristine B
KB
Chen
Ya-Chi
YC
Rezk
Naser L
NL
Fiscus
Susan A
SA
Kearney
Brian P
BP
Rooney
James F
JF
Hui
James
J
Cohen
Myron S
MS
Kashuba
Angela D M
AD
D000225:Adenine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D005837:Genitalia, Male / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry; D000068698:Tenofovir
D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D000068698:Tenofovir; D000225:Adenine