Single and Multiple Dose Pharmacokinetics of Maraviroc in Saliva, Semen, and Rectal Tissue of Healthy HIV-Negative Men
ABSTRACT Antiretroviral pharmacology in seminal plasma (SP) and rectal tissue (RT) may provide insight into antiretroviral resistance and the prevention of sexual transmission of human immunodeficiency virus (HIV). Saliva may be of utility for noninvasively measuring adherence.
A pharmacokinetic study was performed in 12 HIV-negative men receiving maraviroc 300 mg twice daily for 8 days. Seven time-matched pairs of blood plasma (BP) and saliva samples were collected over 12 h on day 1 (PK1) and days 7 and 8 (PK2). One RT sample from each subject was collected during PK1 and PK2. Two SP samples were collected from each subject during PK1, and 6 SP samples were collected from each subject during PK2.
SP AUCs were ∼50% lower than BP. However, protein binding in SP ranged from 4% to 25%, resulting in protein-free concentrations >2-fold higher than BP. RT AUCs were 7.5- to 26-fold higher than BP. Maraviroc saliva AUCs were ∼70% lower than BP, but saliva concentrations correlated with BP (r(2) = 0.58).
More pharmacologically available maraviroc was found in SP than BP. High RT concentrations are promising for preventing rectal HIV acquisition. Saliva correlation with BP suggests that this may be useful for monitoring adherence.
Full-textDOI: · Available from: Kristine B Patterson, Sep 28, 2014
- SourceAvailable from: Christian Happi
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ABSTRACT: INTRODUCTION: Maraviroc is the only C-chemokine receptor 5 (CCR5) antagonist approved for the treatment of infection with HIV. This article reviews the safety and efficacy of maraviroc in the treatment of HIV infection. AREAS COVERED: The PubMed database was searched using the keywords 'maraviroc' and 'HIV'. In addition, conference proceedings from CROI, IAS and EACS meetings were searched for maraviroc clinical trials. The PubMed search revealed one Phase IIb - III clinical trial in treatment-naive HIV(+) patients (MERIT) and three Phase IIb - III randomized clinical trials (RCTs) in treatment-experienced patients (MOTIVATE 1 and 2, A4001029). All RCTs showed an excellent safety profile for maraviroc in the treatment of HIV-1 infection. However, long-term (> 3 years) safety data generated on maraviroc therapy are still scarce. Based on the findings from RCTs so far, no relevant toxicities and co-morbidities such as coronary heart disease or hepatotoxicity have been described. The overall CD4(+) cell count increase resulting from a maraviroc-containing regimen appears to be higher than those seen with other antiretroviral regimens. However, the significance remains controversial. To date, maraviroc has shown a potent and durable virological efficacy profile for the treatment of HIV-1 infection. The only use of maraviroc depends on pretreatment testing for CCR5 tropism. EXPERT OPINION: Maraviroc is a generally safe and well-tolerated medication for the treatment of HIV-1 infection with a unique mechanism of action. Long-term (i.e., > 5 years) risks are not known and have to be carefully monitored.Expert Opinion on Drug Safety 11/2011; 11(1):161-74. DOI:10.1517/14740338.2012.640670 · 2.91 Impact Factor