Pharmacokinetics and dromotropic activity of ajmaline in rats with hyperthyroidism
1989
1
The pharmacokinetics and the dromotropic action (increased PQ interval) of intravenously administered adjmaline (2 mg kg−1) were studied in hyperthyroid rats with sinus tachycardia. The hyperthyroidism was induced by intraperitonal injection of 3,5,3′-triiodo-l-thyronine (0.5 mg kg−1) for 4 days.
2
The change in the ajmaline concentration in whole blood could be described by a biexponential equation. The steady state distribution volume of ajmaline decreased from 4.811 kg−1 in control rats to 3.801 kg−1 in hyperthyroid rats and the total body blood clearance was slightly higher in hyperthyroid rats than in control rats.
3
Ajmaline exhibited a saturable binding to rat plasma proteins, and one kind of binding site was found in the observed range of concentrations. The binding capacity was 2 fold higher in hyperthyroid rats than in control rats.
4
On the basis of the plasma unbound concentration, ajmaline exhibited an increased negative dromotropic activity in hyperthyroid rats compared with control rats.
5
A positive correlation was found between the pacing rate and the dromotropic action of ajmaline on atrioventricular conduction in isolated perfused hearts. There was no significant difference in the rate-dependence of the effect of ajmaline on the heart between control and hyperthyroid rats.
6
Our findings suggest that the increased dromotropic activity of ajmaline is mainly due to the increased heart rate in hyperthyroid rats.
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