Pharmacokinetics and dromotropic activity of ajmaline in rats with hyperthyroidism

Abstract

1 The pharmacokinetics and the dromotropic action (increased PQ interval) of intravenously administered adjmaline (2mgkg-1) were studied in hyperthyroid rats with sinus tachycardia. The hyperthyroidism was induced by intraperitonal injection of 3,5,3'-triiodo-L-thyronine (0.5mg kg1) 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' in control rats to 3.801kg-' 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.

Effect of experimental renal dysfunction on bioavailability of ajmaline in rats

“…This investigation was designed to evaluate the bioavailability of a model drug, ajmaline, in rats with nephrotoxic uranyl nitrate-induced acute renal dysfunction. Ajmaline is a Rauwolfia alkaloid with class I antiarrhythmic properties (Bojorges et al 1975 ;Okumura et al 1988 ;Hashimoto et al 1989 ;Padrini et al 1993), and undergoes presystemic clearance after oral administration Yamada et al 1986). We examined the mechanisms responsible for the altered presystemic clearance of ajmaline in renal dysfunction.…”