Validation of Conversion Factors for Therapeutic Drug Monitoring of Lacosamide, Lamotrigine, and Levetiracetam in Dried Capillary Blood.

Abstract

Estimation of serum concentrations of antiseizure medications (ASMs) based on dried capillary blood is an alternative method for therapeutic drug monitoring of epilepsy. The aim of this study was to validate the conversion factors for lacosamide (LCM), lamotrigine (LTG), and levetiracetam (LEV), which were determined in an independent patient sample in a previous study, and identify the most accurate conversion method (simple ratio and regression). Venous and capillary blood samples were collected from adult inpatients with epilepsy treated with LCM (n = 25), LTG (n = 27), and/or LEV (n = 29) before the morning dose (T1) and approximately 2 hours after (T2). Capillary blood was collected using volumetric absorptive microsampling, and the ASM concentrations were measured using a validated liquid chromatography-mass spectrometry method for dried blood samples. Serum concentrations were estimated using conversion factors and compared with those measured using routine laboratory methods. For all 3 ASMs, the simple ratio approach performed better than the regression approach. Intraclass correlation coefficients revealed a high agreement between the estimated and measured serum concentrations (LCM T1: 0.93, T2: 0.90; LTG T1: 0.91, T2: 0.91; and LEV T1: 0.97, T2: 0.94). The criteria of the European Medicines Agency for cross-validation were fulfilled for LCM (T1: 72%; T2: 75%) and LEV (T1: 86%; T2: 75%), whereas for LTG, this was only true for capillary blood concentrations ≤11 µ g/mL [42.9 µ mol/L; T1: 72% (vs. 63% for total range), T2: 67% (vs. 62%)]. Estimating serum concentrations using capillary blood concentrations is feasible and accurate for LCM and LEV over a wide concentration range, as found in clinical practice. The applicability of this mehod for LTG is limited by its greater variability at higher concentrations; however, acceptable results were achieved for the large proportion of patients with low and medium LTG concentrations.