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

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 51; no. 5; p. 546
• Main Authors: Dumond, Julie B, Patterson, Kristine B, Pecha, Allison L, Werner, Rebecca E, Andrews, Emma, Damle, Bharat, Tressler, Randall, Worsley, Jochen, Kashuba, Angela D M
• Format: Journal Article
• Language: English
• Published: United States 01.08.2009
• Subjects: Adolescent; Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - blood; Anti-HIV Agents - pharmacokinetics; CCR5 Receptor Antagonists; Cervix Uteri - metabolism; Cyclohexanes - administration & dosage; Cyclohexanes - blood; Cyclohexanes - pharmacokinetics; Female; HIV Infections - prevention & control; HIV Infections - transmission; HIV Seronegativity - physiology; HIV-1; Humans; Maraviroc; Middle Aged; Protein Binding; Triazoles - administration & dosage; Triazoles - blood; Triazoles - pharmacokinetics; Vagina - metabolism; Young Adult
• ISSN: 1525-4135
• DOI: 10.1097/QAI.0b013e3181ae69c5

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. Open-label pharmacokinetic study. 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. 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. 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.