The pharmacodynamics of bucainide (RHC G233): pharmacokinetic parameters and relationship between plasma levels and the effect on the electrocardiogram in the dog.

The pharmacodynamic profile of bucainide dimaleate (RHC G-233) in dogs has been studied. The first observed pharmacologic effect was a change in the ECG pattern (T-wave duration and amplitude) that occurred after an average intravenous dose of 2.7 mg/kg. The average plasma concentration of bucainide was approximately 350 ng/ml. Analysis of data from dogs that received a dual infusion of bucainide indicated that bucainide has an extensive volume of distribution, with an average value of approximately 26 l/kg. An average terminal half-life of 89 minutes was observed. Studies with the radiolabeled drug in rats and dogs also demonstrated the drug's large volume of distribution, and its initial rapid disappearance from the blood. Tissue distribution studies in the rat after administration of the radiolabeled drug showed that bucainide is rapidly taken up by the tissues.