title: Brief Report: Pharmacokinetic/Pharmacodynamic Investigation of Single-Dose Oral Maraviroc in the Context of HIV-1 Pre-exposure Prophylaxis.
abstract: To investigate the pharmacokinetics/pharmacodynamics of single-dose maraviroc 300 mg in HIV-1 exposure compartments. Maraviroc concentrations in blood, secretions (vaginal, urethral, oral, and rectal), and tissue (vaginal and rectal) were measured, and ex vivo challenge was performed in 54 healthy volunteers to study protection from HIV infection. Maraviroc Cmax occurred within 4 hours in most compartments. Concentrations from 4 to 72 hours were above intracellular (IC) IC90 in all compartments, range 15-8095 ng/mL. Mean AUC0-72 compartment-to-plasma ratios were highest in the rectum (45-819) and urethra (144) compared with the female genital tract (1.6-4.8) and saliva (0.2). No sex differences in AUC0-72 or Cmax were observed. No ex vivo protection from HIV-1BaL occurred in rectal or vaginal tissue. Despite high and sustained concentrations, single-dose maraviroc was not protective against ex vivo challenge of vaginal/rectal tissue.
authors.affiliation: *Guys and St. Thomas' NHS Foundation Trust, London, United Kingdom; †Imperial College London, London, United Kingdom; ‡University of Liverpool, Liverpool, United Kingdom; and §St Stephen's Centre, Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom.
authors.forename: Julie
authors.initials: J
authors.lastname: Fox
authors.forename: Juan M
authors.initials: JM
authors.lastname: Tiraboschi
authors.forename: Carolina
authors.initials: C
authors.lastname: Herrera
authors.forename: Laura
authors.initials: L
authors.lastname: Else
authors.forename: Deirdre
authors.initials: D
authors.lastname: Egan
authors.forename: Laura
authors.initials: L
authors.lastname: Dickinson
authors.forename: Akil
authors.initials: A
authors.lastname: Jackson
authors.forename: Natalia
authors.initials: N
authors.lastname: Olejniczak
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.forename: Saye
authors.initials: S
authors.lastname: Khoo
authors.forename: Robin
authors.initials: R
authors.lastname: Shattock
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
mesh_terms: D000284:Administration, Oral; D000328:Adult; D065100:CCR5 Receptor Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D003510:Cyclohexanes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects; D064368:Healthy Volunteers; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000821:virology; D008297:Male; D000077592:Maraviroc; D008954:Models, Biological; D065129:Pre-Exposure Prophylaxis; D016032:Randomized Controlled Trials as Topic; D012007:Rectum / Q000187:drug effects / Q000821:virology; D012463:Saliva / Q000187:drug effects / Q000821:virology; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D014521:Urethra / Q000187:drug effects / Q000821:virology; D014621:Vagina / Q000187:drug effects / Q000821:virology
chemical_list: D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D014230:Triazoles; D000077592:Maraviroc