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.
Design: 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 AUCτ 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 AUCτ 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.
From the *Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill Eshelman School of Pharmacy, Chapel Hill, NC; †Department of Medicine, Infectious Diseases Division, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC; and ‡Pfizer Global Research and Development, New York, NY.
Received for publication September 15, 2008; accepted February 17, 2009.
Supported by National Institute of Allergy and Infectious Disease/National Institutes of Health (AI54980, ADMK; AI77355, KBP), Building Interdisciplinary Careers in Women's Health (HD001441, KBP), University of North Carolina at Chapel Hill (UNC) Center for AIDS Research (AI50410), UNC General Clinical Research Center (RR00046), and Pfizer Global Research and Development.
Data presented previously at the 15th Conference on Retroviruses and Opportunistic Infections, February 3-6, 2008, Boston, MA (Abstract 135LB).
Correspondence to: Angela D. M. Kashuba, BScPharm, PharmD, DABCP, University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, 3318 Kerr Hall, CB #7360, Chapel Hill, NC 27599-7360 (e-mail: firstname.lastname@example.org).