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J Acquir Immune Defic Syndr. 2009 Aug 15;51(5):546-53. doi: 10.1097/QAI.0b013e3181ae69c5.

Maraviroc concentrates in the cervicovaginal fluid and vaginal tissue of HIV-negative women.

Author information

1
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill Eshelman School of Pharmacy, Chapel Hill, NC 27599-7360, USA.

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.

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 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.

PMID:
19546811
PMCID:
PMC2751766
DOI:
10.1097/QAI.0b013e3181ae69c5
[Indexed for MEDLINE]
Free PMC Article

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