Relatie tussen farmacokinetiek van ajmaline en ST-elevatie bij de diagnostiek van het Brugada-syndroom

Abstract

OBJECTIVE To investigate the relationship between ajmaline serum levels (pharmacokinetics, PK) and changes in the ST segment on the electrocardiogram (pharmacodynamics, PD) in patients with suspected Brugada syndrome (BS). DESIGN AND METHODS We determined the PK profile of ajmaline in 34 patients referred to the cardiology clinic for diagnosis of Brugada syndrome. The PD profile was derived from the ST elevations on the electrocardiograms of 26 patients during the diagnostics of BS. The PK and PD data were examined and fitted into non-linear mixed effect modelling (NONMEM 7). The final PK model was evaluated with data from 8 newly included patients. RESULTS Pharmacokinetics of ajmaline was best described with a two compartment model and the PK/PD data as a direct effect with a linear relationship between ajmaline serum levels and ST segment elevation. In BS-positive patients the baseline ST segment was 0.06 mV (rsd 35%) with a slope of 0.03 mV•mL/mg (rsd 94%). In BS-negative patients no association was found between ajmaline serum levels and ST segment elevation. CONCLUSION Pharmacokinetics of ajmaline in patients with suspected BS is best described with a two compartment model with linear elimination. A direct association between ajmaline serum levels and ST segment elevation in BS-positive patients was found. No association was found between ajmaline serum levels and ST segment elevation in BSnegative patients. In future studies this model can be used to examine the effects of co-variates in order to optimize the use of ajmaline in the diagnosis of BS