Mechanisms of pharmacokinetic interaction between ajmaline and quinidine in rats.

In order to elucidate the mechanism of ajmaline-quinidine interaction previously observed in humans, the effects of quinidine on pharmacokinetics of ajmaline were investigated in rats. Concurrent oral administration of 10 mg/kg of quinidine markedly increased the plasma concentration of ajmaline at a dose of 2 mg/kg. On the other hand, it did not affect the pharmacokinetics of ajmaline after intravenous dose. The availability of ajmaline after oral dose showed an increase from 13% to nearly 100% by the presence of quinidine, which suggests a change in the presystemic clearance of ajmaline. In fact, when ajmaline was administered into the intestinal loop, its concentration in mesenteric venous plasma increased approximately 5-fold by the combination with quinidine. Furthermore, quinidine delayed the elimination rate of ajmaline from the perfused rat liver. These results indicate that quinidine prevents presystemic elimination of ajmaline in the intestine and liver, and increases the systemic availability of ajmaline.