Maraviroc concentrates in the cervicovaginal fluid and vaginal tissue of HIV-negative women.
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.
Dumond
Julie B
JB
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill Eshelman School of Pharmacy, Chapel Hill, NC 27599-7360, USA.
Patterson
Kristine B
KB
Pecha
Allison L
AL
Werner
Rebecca E
RE
Andrews
Emma
E
Damle
Bharat
B
Tressler
Randall
R
Worsley
Jochen
J
Kashuba
Angela D M
AD
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
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc