title: Single and multiple dose pharmacokinetics of maraviroc in saliva, semen, and rectal tissue of healthy HIV-negative men.
abstract: BACKGROUND
  Antiretroviral pharmacology in seminal plasma (SP) and rectal tissue (RT) may provide insight into antiretroviral resistance and the prevention of sexual transmission of human immunodeficiency virus (HIV). Saliva may be of utility for noninvasively measuring adherence.
  
  
  METHODS
  A pharmacokinetic study was performed in 12 HIV-negative men receiving maraviroc 300 mg twice daily for 8 days. Seven time-matched pairs of blood plasma (BP) and saliva samples were collected over 12 h on day 1 (PK1) and days 7 and 8 (PK2). One RT sample from each subject was collected during PK1 and PK2. Two SP samples were collected from each subject during PK1, and 6 SP samples were collected from each subject during PK2.
  
  
  RESULTS
  SP AUCs were ∼50% lower than BP. However, protein binding in SP ranged from 4% to 25%, resulting in protein-free concentrations >2-fold higher than BP. RT AUCs were 7.5- to 26-fold higher than BP. Maraviroc saliva AUCs were ∼70% lower than BP, but saliva concentrations correlated with BP (r(2) = 0.58).
  
  
  CONCLUSIONS
  More pharmacologically available maraviroc was found in SP than BP. High RT concentrations are promising for preventing rectal HIV acquisition. Saliva correlation with BP suggests that this may be useful for monitoring adherence.
  
  
  BACKGROUND
  NCT00775294.
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7569, USA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Brown
authors.forename: Kristine B
authors.initials: KB
authors.lastname: Patterson
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Malone
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shaheen
authors.forename: Heather M Asher
authors.initials: HM
authors.lastname: Prince
authors.forename: Julie B
authors.initials: JB
authors.lastname: Dumond
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Spacek
authors.forename: Paris E
authors.initials: PE
authors.lastname: Heidt
authors.forename: Myron S
authors.initials: MS
authors.lastname: Cohen
authors.forename: Angela D M
authors.initials: AD
authors.lastname: Kashuba
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003510:Cyclohexanes / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D000077592:Maraviroc; D012007:Rectum / Q000378:metabolism*; D012463:Saliva / Q000737:chemistry*; D012661:Semen / Q000737:chemistry*; D014230:Triazoles / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc