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.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.
"Unfortunately this biological matrix is infrequently used despite its potential usefulness. In recent times however, there has been increased interest in the use of this alternative matrix for drug treatment testing [12,13,19]. The need for the use of oral fluid in therapeutic monitoring of anti-malarial drugs in resource poor malaria endemic regions cannot be overemphasized. "
[Show abstract][Hide abstract] ABSTRACT: Mefloquine-artesunate is a formulation of artemisinin based combination therapy (ACT) recommended by the World Health Organization and historically the first ACT used clinically. The use of ACT demands constant monitoring of therapeutic efficacies and drug levels, in order to ensure that optimum drug exposure is achieved and detect reduced susceptibility to these drugs. Quantification of anti-malarial drugs in biological fluids other than blood would provide a more readily applicable method of therapeutic drug monitoring in developing endemic countries. Efforts in this study were devoted to the development of a simple, field applicable, non-invasive method for assay of mefloquine in saliva.
A high performance liquid chromatographic method with UV detection at 220 nm for assaying mefloquine in saliva was developed and validated by comparing mefloquine concentrations in saliva and plasma samples from four healthy volunteers who received single oral dose of mefloquine. Verapamil was used as internal standard. Chromatographic separation was achieved using a Hypersil ODS column.
Extraction recoveries of mefloquine in plasma or saliva were 76-86% or 83-93% respectively. Limit of quantification of mefloquine was 20 ng/ml. Agreement between salivary and plasma mefloquine concentrations was satisfactory (r = 0.88, p < 0.001). Saliva:plasma concentrations ratio was 0.42.
Disposition of mefloquine in saliva paralleled that in plasma, making salivary quantification of mefloquine potentially useful in therapeutic drug monitoring.
[Show abstract][Hide abstract] ABSTRACT: To prevent acquisition of HIV through oral sex, drugs used for preexposure prophylaxis (Prep) need to diffuse in saliva. We measured tenofovir (TFV) and emtricitabine (FTC) concentrations simultaneously in the plasma and saliva of 41 HIV-infected patients under stable antiretroviral treatment. Mean ratios of saliva/plasma concentration were 3% (±4%) and 86.9% (±124%) for TFV and FTC, respectively. Tenofovir disoproxil fumarate (TDF) should be used in combination with FTC to prevent oral acquisition of HIV.
[Show abstract][Hide abstract] 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