Abstract
An analysis of the serum and salivary concentration after procainamide (PA) adminis-tration was first carried out and an attempt was made to determine the relationship between pharmacokinetics and anti-arrhythmic effect of the PA in patients with premature ventricular contractions (PVCs). Five hundred mg of PA was given orally to 4 healthy volunteers. In chronic oral administration study, maintenance dose of PA was adminis-tered repeatedly in every half-life of PA. In patients with PVCs, 500 mg of PA was injected intravenously and 1000 mg of PA was administered orally. Blood and salivary samples were collected at regular intervals. Blood and salivary concentration of PA and its active metabolite, N-acetylprocainamide (NAPA), were determined fluorometrically. In oral administration study, blood concentration data was analyzed using adequate compartment models. After single oral administration of PA to normal subjects, the salivary concentrations of PA and NAPA were approximately twice higher than the serum concentration of PA and NAPA. The saliva to serum concentration ratios of PA and NAPA kept at constant values during elimination phase. There was a significant correlation between serum and salivary concentration of PA (r=0.89, p<9.001) and NAPA (1=0.87, p<0.001) in both single and chronic oral administration studies. In patients with PVCs, significant correlation between QTc prolongation induced by PA and its serum concentration was seen. A significant correlation (r=0.69, P<0.001) between the percent decrease of PVCs and serum PA concentration was also observed after intravenous injection of PA.
