Pharmacokinetics and antiarrhythmic activity of ajmaline in rats subjected to coronary artery occlusion.
The pharmacokinetics and the antiarrhythmic action of intravenous ajmaline were investigated in anaesthetized rats subjected to coronary artery occlusion. Ajmaline (0.125-2 mg kg-1, i.v. given just after occlusion) suppressed arrhythmias in a dose-dependent manner, judged by the reduction of premature ventricular complexes. The incidence of malignant arrhythmias (ventricular tachycardia and fibrillation) was preferentially suppressed at the higher doses of ajmaline (1 and 2 mg kg-1). Coronary occlusion induced a change in pharmacokinetics of ajmaline (2 mg kg-1) and its total body blood clearance was significantly decreased from 56.6 ml min-1 kg-1 in sham-operated rats to 43.1 ml min-1 kg-1 in rats after coronary occlusion. Ajmaline exhibited a significantly increased negative dromotropic action (increased PQ interval) in rats after coronary occlusion compared with that in sham-operated rats. The difference seems to be due to the pharmacokinetic change since the concentration-effect relationship was similar in the two groups of rats. We suggest that the measurement of drug levels is important in the assessment of antiarrhythmic agents.
Hashimoto
Y
Y
Hori
R
R
Okumura
K
K
Yasuhara
M
M
D000404:Ajmaline / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D004562:Electrocardiography; D004798:Enzymes / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000889:Anti-Arrhythmia Agents; D004798:Enzymes; D000404:Ajmaline