THE EFFECTS OF INFUSION RATE OF CHANGROLIN ON DRUG CONCENTRATION IN BLOOD AND ECG

Changrolin is a new antiarrhythmic drug discovered by our institute. It has an inhibitory effect on the myocardial electrical conduction. The purpose of this paper is to report the effects of 3 different infusion rates (group A: 5mg/kg/min for 2 min; group B: 1mg/kg/min for 30min; group C: 0.13 mg/kg/min for 120 min) on the plasma drug concentration and ECG changes in anesthesized dogs.The low infusion rate of C group possesses a lot of benefits: It can avoid the abrupt ascending and. descending of the drug concentration in blood, which are observed in group A. The ECG changes are lighter, ahhough the total dosage is higher than group A by 1/2 times. In comparison with group B, the total dosage of group C is only one half of that of group B, but the drug concentration in blood is maintained at a definite level for a longer time. Therefore, it is advisable to use the low infusion rate in the clinic.During the course of infusion in group C, the heart rate increased slightly at the beginning. And, as the drug concentration rose to above 5μg/ml, the heart rate decreased gradually and the ECG changed with a prolongation of P-R interval and a widening of QRS complex. These exhibitions are "quinidine-like". The linear relations of the plasma Changrolin concentration to the length of P-R interval and to the width of QRS obey the following mathematical equations:Y₁=0.00484X+0.0652Y₂=0.00190X+0.0456 where Y₁ is the length of P-R interval, Y₂ is the width of QRS complex and X is the plasma Changrolin concentration.From these 2 equations, it can be shown that the A-V conduction is more sensitive to Changrolin than intraventricular conduction.At the drug concentration lower than 8μg/ml, the changes of the ECG did not exceed the first degree block.