ABSTRACT
BACKGROUND: Measurement of drug levels in plasma is currently the gold standard for pharmacological studies. However, venous sampling is not feasible in some populations (e.g., neonates) or may be difficult in certain situations, such as nonhospital-based settings. Dried blood spots (DBS) can be obtained by a simple fingerprick and the subsequent collection of blood on a filter card, allowing patient-friendly sample collection in non-hospital-based settings. Despite these advantages, thus far no clinical evaluation has been performed for the use of DBS concentrations as surrogates for plasma levels. Our purpose was to clinically evaluate DBS sampling for the determination of plasma concentrations for the novel antiretroviral drugs etravirine, darunavir/ritonavir and raltegravir. RESULTS: DBS concentrations were measured in 11 HIV-infected patients using LC-MS/MS. DBS concentrations were proportional to plasma concentrations. All drug concentrations were higher in DBS than in plasma samples. The plasma:DBS ratio and the respective relative standard error of estimate (RSE) of darunavir, etravirine, raltegravir and ritonavir were 0.632 (4.97% RSE), 0.523 (4.84% RSE), 0.617 (14.9% RSE) and 0.592 (2.99% RSE), respectively. Hematocrit did not explain variability in our study. CONCLUSIONS: DBS are reproducibly correlated to plasma levels and can be used for monitoring antiretroviral drug exposure in HIV-infected patients.
Subject(s)
Chromatography, High Pressure Liquid/methods , HIV Protease Inhibitors/blood , Mass Spectrometry/methods , Blood Specimen Collection , Darunavir , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , Humans , Male , Middle Aged , Nitriles , Pyridazines/blood , Pyridazines/therapeutic use , Pyrimidines , Pyrrolidinones/blood , Pyrrolidinones/therapeutic use , Raltegravir Potassium , Ritonavir/blood , Ritonavir/therapeutic use , Sulfonamides/blood , Sulfonamides/therapeutic useABSTRACT
In this study, we present a case of renal failure in a patient who was on a tenofovir-containing regimen, resulting in extremely high tenofovir exposure and prolonged tenofovir monotherapy. We considered this case report important because exposure to tenofovir monotherapy might have consequences for future discontinuation strategies in cases of renal failure.
