抄録
The purpose . of the present study was to evaluate the pharmacokinetic interaction between nifedipine and quinidine sulfate. To investigate any potential interaction, 6 male beagle dogs orally received 10 mg nifedipine or the combination of 10 mg nifedipine and 100 mg quinidine sulfate. These investigations were done using a randomized cross-over study design with a one-week wash-out period between treatments. Following the oral administration of nifedipine, the maximum serum concentration of nifedipine was signifi cantly increased by coadministration of quinidine sulfate. The mean residence time was significantly reduced by coadministration of quinidine sulfate. The dogs then received intravenously 4 mg nifedipine withor without 100 mg of oral quinidine sulfate . Following intravenous administration of nifedipine, the volume of distribution was significantly reduced, and the elimination rate constant was significantly increased by coadministra tion of quinidine sulfate.
The effects of quinidine sulfate on the metabolism of nifedipine to metabolite (M-1) were studied using dog liver microsomes. Quinidine sulfate inhibited microsomal nifedipine oxidation in a noncompetitive manner. To determine whether quinidine sulfate interferes with the protein binding of nifedipine in vitro, the free fraction of nifedipine was determined by an ultracentrifugation technique. These data indicate that quinidine sulfate inhibits the binding of nifedipine to human albumin and α1-acid glycoprotein in a competitive manner. The results of the in vitro experiments suggest that quinidine sulfate inhibits the hepatic first pass metabolism and the serum protein binding of nifedipine. This pharmacokinetic interaction may result in an enhanced pharmacologic response.
