Dried Blood Spot Analysis Suitable for Therapeutic Drug Monitoring of Voriconazole, Fluconazole, and Posaconazole

Abstract

e Invasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of the pharmacokinetics of the triazoles among and within individual patients, therapeutic drug monitoring is important for optimizing the efficacy and safety of antifungal treatment. A dried blood spot (DBS) analysis was developed and was clinically validated for voriconazole, fluconazole, and posaconazole in 28 patients. Furthermore, a questionnaire was administered to evaluate the patients' opinions of the sampling method. The DBS analytical method showed linearity over the concentration range measured for all triazoles. Results for accuracy and precision were within accepted ranges; samples were stable at room temperature for at least 12 days; and different hematocrit values and blood spot volumes had no significant influence. The ratio of the drug concentration in DBS samples to that in plasma was 1.0 for voriconazole and fluconazole and 0.9 for posaconazole. Sixty percent of the patients preferred DBS analysis as a sampling method; 15% preferred venous blood sampling; and 25% had no preferred method. There was significantly less perception of pain with the DBS sampling method (P ‫؍‬ 0.021). In conclusion, DBS analysis is a reliable alternative to venous blood sampling and can be used for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole. Patients were satisfied with DBS sampling and had less pain than with venous sampling. Most patients preferred DBS sampling to venous blood sampling.

Cost Evaluation of Dried Blood Spot Home Sampling as Compared to Conventional Sampling for Therapeutic Drug Monitoring in Children

“…Whether DBS home sampling is more efficient, depends on the accuracy and precision of the DBS assay compared to the conventional (plasma) assay [27–30]. Alongside our clinical study on efficacy of DBS sampling, a cost-effectiveness of DBS home sampling is performed.…”

Therapeutic drug monitoring of tacrolimus and mycophenolic acid in outpatient renal transplant recipients using a volumetric dried blood spot sampling device

“…Correction of DBS concentrations is performed based on the patientspecific or average haematocrit, often in combination with the red blood cell to plasma partition ratio [25,26]. Translation strategies without haematocrit correction are performed based on the average DBS to WB or plasma ratio [21,44,45] or the DBS to WB or plasma concentration regression fit slope or equation [44,[46][47][48][49]. To investigate the need for and extent of correction of tacrolimus and mycophenolic acid DBS concentrations in the present study, a clinical pilot study was conducted from February to June 2016.…”

Procedures and Practices for The Validation of Bioanalytical Methods Using Dried Blood Spots: A Review

“…There are large differences in the extent to which the influence of Hct is investigated. Especially the more recent papers describe the investigation of a broad range of Hct values, specifically, at least between 20 and 50% [15,18,23,37,39,55,73,74,77,83,86,87,89,90], usually evaluated at two concentration levels. The majority of the reports investigating the effect of Hct on assay performance describe a trend that Hct value is positively related to measured analyte concentration.…”