Pharmacokinetics and Antiarrhythmic Activity of Ajmaline in Rats Subjected to Coronary Artery Occlusion

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1986 May 1

PMID 3708225

Citations 4

Authors

Y Hashimoto

R Hori

K Okumura

M Yasuhara

Affiliations

Soon will be listed here.

Abstract

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.

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