ANTIARRHYTHMIC EFFECT RELATED TO THE PLASMA-CONCENTRATION OF PENTISOMIDE IN-VIVO AND THE ANTIARRHYTHMIC-CONCENTRATION RELATIONSHIP IN-VITRO

Pentisomide, ropylaminoethyl)-4-methyl-2-(pyridyl)-pentanamide, is a n ovel anti-arrhythmic agent structurally related to disopyramide. Using a glass bead arrhythmic model, the authors studied the antiarrhythmic effect of pentisomide in dogs by monitoring the plasma concentrations . When pentisomide was infused at 1 mg/kg/min for 20 min, the ventricu lar tachycardia was significantly reduced at 5 min after starling the infusion, the arrhythmias were reduced to less than 5% at the end of t he 20 min infusion. The plasma-free concentration of pentisomide was a bout 3 mu g/ml at 5 min; it increased to about 10 mu g/ml at the end o f 20 min infusion. With 0.3 mg/kg/min infusion, the arrhythmias were r educed to about 60% but were not significant at 20 min of infusion. Th e plasma-free concentration of pentisomide did not reach 3 mu g/ml unt il 20 min of infusion. The 3 mu g/ml plasma-free concentration for pen tisomide seems to be a critical concentration in inducing a significan t antiarrhythmic effect. Pentisomide dose-dependently inhibited ischae mia-reperfusion arrhythmia al doses of 30 mu M and higher concentratio ns in vitro. In conclusion, pentisomide inhibits arrhythmias dependent with the plasma concentration or with the concentration of the extern al solution. The critical plasma-free concentration for inhibition of arrhythmias was 3 mu g/ml (is approximately equal to 10 mu M) and the in vitro effect also had a similar concentration. Therefore, the in vi vo and in vitro antiarrhythmic concentrations were well correlated.