Pharmacokinetics and electrophysiological effects of intravenous ajmaline.
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)
Padrini
R
R
Department of Pharmacology, University of Padua, Italy.
Piovan
D
D
Javarnaro
A
A
Cucchini
F
F
Ferrari
M
M
D000368:Aged; D000404:Ajmaline / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006327:Heart Block / Q000175:diagnosis; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged
D000404:Ajmaline