COMBINED PHARMACOKINETIC—PHARMACODYNAMIC MODEL OF PROCAINAMIDE IN RABBITS WITH IN-DUCED VENTRICULAR FIBRILLATION THRESHOD (VFT) CHANGES

The change of electrically induced VFT was chosen as index of effect in anesthetized rabbits for study of pharmacodynamics of PA and NAPA. We analyzed the pharmacokinetic propertics of PA and NAPA and elucidated tbeir offect kinetics with a pharmacokinetic-pharmacodynamic (PK/PD) model in view of different transfer qualities. A linear-addition effect model was used to describe the relationship between the effect and the amount of drug and its metabolite in the effect compartment. PA was found to be eliminated faster than NAPA and distributed more extensively in rabbits. The effect per unit concentration of PA was shown to be larger than that of NAPA.