Preclinieal Pharmacodynamic Studies And Safety Evaluations Of Isoquinoline New Drugs

Isoquinoline new drugs is a novel chiral compound with strong anti-arrhythmic activity selected from a series of target anti-arrhythmic agents(Code:HQ1127). This study focused on the anti-arrhythmic effect of HQ 1127; the in vivo pharmacokinetic character in rats has been investigated and primary safety evaluation has been provided.Pharmacodynamic study shows that HQ1127 has effects on wide ranges of cardiac arrhythmias induced by different mechanisms; it has good preventive effect on myocardial ischemia-reperfusion injury in rats induced by ligation and acute myocardial ischemia in rats induced by Pituitrin. The preclinical preliminary pharmacokinetic study has showed elimination half-life and clearance rate are 1.09 h and 7.29 L/hr respectively when administered i.v.; AUC(0-∞) is 738.31 ug*hr/L; T1/2 and AUC(0-∞) are 50 h and 1436.42 ug*hr/L respectively after administered i.g.; Tmax and Cmax have been observed at 0.21 h and 1808.47ug/L respectively; bioavailability by p.o. gives the figure 48.6%; both half-life and clearance rate meet the requirement of medical products designing. HQ1127 has given low clearance rate in liver microsomal metabolic stability test, showing it is stable during metabolism. Preclinical primary safety evaluation result indicates that HQ1127 has a wide safety range, since no toxicity has been observed at the level 50 times of the effective does.