Pharmacokinetics and Electrophysiological Effects of Intravenous Ajmaline

Abstract

The pharmacokinetics of ajmaline were studied in 10 patients with suspected paroxysmal atrioventricular block who received a 1 mg/kg intravenous dose over 2 minutes for diagnostic purposes (ajmaline test). Plasma concentration decay followed a triexponential time course with a final half-life much longer (7.3 +/- 3.6 hours) than that previously found by other investigators (about 15 minutes). Mean total plasma clearance and renal clearance were 9.76 ml/min/kg and 0.028 ml/min/kg, respectively. Although most of the dose was eliminated through the extrarenal route (only 3.5% of the intravenous dose was recovered in urine), no fluorescent metabolites could be detected either in plasma or urine. The steady-state volume of distribution averaged 6.17 L/kg, and plasma protein binding ranged between 29 and 46%. Three patients developed a transient atrioventricular block after ajmaline administration. In the remainder, the drug prolonged atrio-His bundle (AH interval), His bundle-ventricular (HV interval) and intraventricular (QRS interval) conduction times. Corrected ventricular repolarisation time (QTc interval) showed less marked changes, which were biphasic at times. The mean maximum ajmaline-induced increase in HV interval was 98%, in QRS was 58%, in AH was 30%, and in QTc was 17%. In most cases the time course of electrocardiographic changes lagged behind that of plasma concentrations, suggesting a delayed equilibrium of plasma concentrations with the site of action (hysteresis). Despite that, the pharmacokinetic-pharmacodynamic model, which accounted for hysteresis, failed to fit the experimental data adequately.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of experimental renal dysfunction on bioavailability of ajmaline in rats

“…This investigation was designed to evaluate the bioavailability of a model drug, ajmaline, in rats with nephrotoxic uranyl nitrate-induced acute renal dysfunction. Ajmaline is a Rauwolfia alkaloid with class I antiarrhythmic properties (Bojorges et al 1975 ;Okumura et al 1988 ;Hashimoto et al 1989 ;Padrini et al 1993), and undergoes presystemic clearance after oral administration Yamada et al 1986). We examined the mechanisms responsible for the altered presystemic clearance of ajmaline in renal dysfunction.…”

Ajmaline Challenge in Young Individuals with Suspected Brugada Syndrome

“…Provocative pharmacological test with intravenous application of sodium channel blockers (ajmaline or flecainide mainly) has been proposed for the first time in 2000 7 and thereafter widely applied 8 to improve the identification of BS in patients suspected to be carriers of the disease. Ajmaline is available only for intravenous infusion due to its poor oral bioavailability and is supposed to be the best drug to unmask BS, both because of its kinetics and strength of rate‐dependent sodium channel blocking effects and because of a short half‐life and brief duration of its electrophysiological effects (minutes), which gives it a clinical advantage compared to other antiarrhythmic drugs 9 …”

Usefulness of patient’s history and non-invasive electrocardiographic parameters in prediction of ajmaline test results in patients with suspected Brugada syndrome

“…Another reason for choosing ajmaline was its short half-life (approximately 10 min) [15] which allows for a short time of monitoring after the test and thus provides a safe way to conduct the test during the patient's 1-day stay in the department.…”