Pharmacokinetics of ajmaline in diagnosis of Brugada syndrome: New data for an old drug

Aims: We sought to obtain new insight into the pharmacokinetics of ajmaline by studying the serum levels of this drug in patients with suspected Brugada syndrome. Ajmaline is a sodium channel blocking, class 1A anti-arrhythmic drug. It has gained renewed interest in the field of cardiology as a diagnostic agent to reveal the electrocardiographic characteristics in patients with suspected Brugada syndrome. Methods: We determined the pharmacokinetic profile of ajmaline in 36 consecutive patients referred to our university hospital's cardiology clinic for diagnosis of Brugada syndrome (Table 1). Ajmaline was administered as incremental 10 mg bolus injections to a total of 1 mg/kg body weight followed by a continuous infusion in 4 increasing dosage regimens for several minutes. Infusion was stopped following judgement of the electrocardiographic parameters by the cardiologist with respect to the diagnostic criteria of Brugada syndrome [1]. Four to twelve blood samples were drawn from a vein of the opposite arm into which ajmaline was administered intravenously. Analysis of serum ajmaline levels was performed with a reversed phase liquid chromatographic method and fluorimetric detection in a previously published assay. Serum concentrations of ajmaline were fitted into a Bayesian pharmacokinetic program (MW Pharm 3.50; MediWare, Groningen, Netherlands). Pharmacokinetic data were compared to the literature. Results: Pharmacokinetics of ajmaline was best described with a three compartimental model. Serum concentration decay followed a triexponential time course with half-lifes of 0,40 € 0,04, 5,43 € 0,14 and 59,19 € 20,73 (h) for the a-, b- and gelimination phases. Clearance was 10,69 € 1,16 (L/h) and total volume of distribution was 12,38 € 4,65 (L/kg) and 2,79 € 1,21 (L/kg) in the first compartment (Table 2). Conclusion: This study showed that pharmacokinetics of ajmaline in patients with suspected Brugada syndrome did not differ from earlier reported pharmacokinetic data of this drug. These renewed data on the pharmacokinetics of ajmaline can further improve diagnostic testing of Brugada syndrome with respect to optimal ajmaline dosing. (Table presented) body clearance, V = volume of distribution, V 1 = volume of distribution of central compartment.