title: The pharmacokinetics and viral activity of tenofovir in the male genital tract.
abstract: 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.
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina, Chapel Hill , NC 27599-7360, USA.
authors.forename: Manoli
authors.initials: M
authors.lastname: Vourvahis
authors.forename: Hiba L
authors.initials: HL
authors.lastname: Tappouni
authors.forename: Kristine B
authors.initials: KB
authors.lastname: Patterson
authors.forename: Ya-Chi
authors.initials: YC
authors.lastname: Chen
authors.forename: Naser L
authors.initials: NL
authors.lastname: Rezk
authors.forename: Susan A
authors.initials: SA
authors.lastname: Fiscus
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kearney
authors.forename: James F
authors.initials: JF
authors.lastname: Rooney
authors.forename: James
authors.initials: J
authors.lastname: Hui
authors.forename: Myron S
authors.initials: MS
authors.lastname: Cohen
authors.forename: Angela D M
authors.initials: AD
authors.lastname: Kashuba
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D000068698:Tenofovir; D000225:Adenine