Kinetic Analysis of the Vasodilator and Ganglionic Blocking Actions of N-Acetylprocainamide

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Abstract
Summary The hypotensive effects of N-acetylprocainamide (NAPA) were studied in anesthetized dogs and in a normal subject. In dogs, intravenous NAPA infusions reduced mean arterial pressure and the pressor response of the isolated, perfused gracilis muscle vascular bed to preganglionic, but not postganglionic, sympathetic stimulation. The kinetics of these effects were correlated with NAPA pharmacokinetics. The time course of NAPA concentrations in a hypothetical biophase was characterized, and the relationship between NAPA biophase concentrations and the intensity of the effects was determined. From these results, it was estimated that peak effects would occur in dogs 6.6 min after intravenous bolus injection of NAPA, and that biophase NAPA concentrations would lower mean arterial pressure 0.39 mm Hg/μg/ml and would attenuate by 0.224 mm Hg/μg/ml the gracilis muscle vascular bed pressor response to preganglionic stimulation. In the normal subject, a similar analysis indicated that maximal hypotension would occur 8.0 min after intravenous NAPA injection, and that blood pressure would fall 0.40 mm Hg/μg/ml relative to biophase NAPA concentrations. These results suggest that blood pressure should be monitored for at least 10 min after patients receive an intravenous NAPA injection, and that repeated NAPA doses probably should not be administered more frequently.

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