title: Maraviroc concentrates in the cervicovaginal fluid and vaginal tissue of HIV-negative women.
abstract: OBJECTIVE
  To compare single- and multiple-dose maraviroc exposures in cervicovaginal fluid (CVF) and vaginal tissue (VT) with blood plasma (BP) and quantify maraviroc protein binding in CVF.
  
  
  METHODS
  Open-label pharmacokinetic study.
  
  
  METHODS
  In 12 HIV-negative women, 7 paired CVF and BP samples were collected over 12 hours after 1 maraviroc dose. Subjects then received maraviroc twice daily for 7 days. After the last dose, subjects underwent CVF and BP sampling as on day 1, with additional sampling during terminal elimination. VT biopsies were obtained at steady state.
  
  
  RESULTS
  Day 1 and day 7 median maraviroc CVF AUCtau were 1.9- and 2.7-fold higher, respectively, than BP. On day 1, 6 of 12 subjects had detectable maraviroc CVF concentrations within 1 hour; 12 of 12 were detectable within 2 hours, and all exceeded the protein-free IC90. On day 7, maraviroc CVF protein binding was 7.6% and the VT AUCtau was 1.9-fold higher than BP. Maraviroc CVF concentrations 72 hours after dose and BP concentrations 12 hours after dose were similar.
  
  
  CONCLUSIONS
  Higher maraviroc exposure in the female genital tract provides a pharmacologic basis for further evaluation of chemokine receptor 5 antagonists in HIV infection prophylaxis. This is the first study to report antiretroviral VT concentrations, CVF protein binding, and CVF terminal elimination.
authors: Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill Eshelman School of Pharmacy, Chapel Hill, NC 27599-7360, USA.
authors: Julie B
authors: JB
authors: Dumond
authors: Kristine B
authors: KB
authors: Patterson
authors: Allison L
authors: AL
authors: Pecha
authors: Rebecca E
authors: RE
authors: Werner
authors: Emma
authors: E
authors: Andrews
authors: Bharat
authors: B
authors: Damle
authors: Randall
authors: R
authors: Tressler
authors: Jochen
authors: J
authors: Worsley
authors: Angela D M
authors: AD
authors: Kashuba
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D065100:CCR5 Receptor Antagonists; D002584:Cervix Uteri / Q000378:metabolism*; D003510:Cyclohexanes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission*; D018023:HIV Seronegativity / Q000502:physiology*; D015497:HIV-1; D006801:Humans; D000077592:Maraviroc; D008875:Middle Aged; D011485:Protein Binding; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014621:Vagina / Q000378:metabolism*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc