Why the study?
Does intravenous ajmaline suppress arrhythmias and how does coronary occlusion affect its pharmacokinetics in rats?
Does intravenous ajmaline suppress arrhythmias and how does coronary occlusion affect its pharmacokinetics in rats?
Coronary occlusion alters the pharmacokinetics of ajmaline in rats, decreasing its clearance and increasing its negative dromotropic effects, highlighting the importance of measuring drug levels when assessing antiarrhythmic agents.
Altered ajmaline pharmacokinetics during ischemia in rats; hypothesis-generating for human dosing studies.
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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Hashimoto et al. (1986) studied this question.
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