Volumetric Absorptive Microsampling for the Therapeutic Drug Monitoring of Everolimus in Patients who have Undergone Liver Transplant

Therapeutic drug monitoring (TDM) of everolimus is required to prevent organ rejection in patients who have undergone transplant. Volumetric absorptive microsampling (VAMS) is a minimally invasive method for accurately collecting a small amount of blood from a patient's fingers. This study aimed to assess the applicability of VAMS for TDM of everolimus.VAMS and venous blood samples were collected from 45 liver transplant recipients who had been receiving stable everolimus doses for at least 7 days. Whole blood everolimus concentrations were measured using ultra-high performance liquid chromatography with tandem mass spectrometry. Deming regression and Bland-Altman analysis were performed to compare everolimus concentrations measured using VAMS (CVAMS) and venous blood samples (CIV). The regression coefficient (r2) between CVAMS and CIV was calculated using a linear regression. The effects of the hematocrit and blood sampling time on the difference between CVAMS and CIV were investigated.Thirty-two participants were included in the final analysis. The Deming regression line was CIV = 1.04*CVAMS + 0.55 (95% confidence interval [CI] of slope, 0.91-1.18; 95% CI of intercept, -0.05 to 1.16). CVAMS and CIV were strongly correlated (r2 = 0.92), with no proportional or constant bias. The mean difference between CVAMS and CIV was -0.79 ng/mL, with the 95% limit of agreement ranging from -2.55 to 0.97 ng/mL in a Bland-Altman plot. No effect of the hematocrit or blood sampling time was observed.VAMS and venous blood sampling showed good agreement for the measurement of whole blood everolimus concentrations. Less invasive VAMS can substitute for more invasive venous blood sampling in the TDM of everolimus in liver transplant patients.