Disposition kinetics of two oral forms of quinidine

Abstract

There are relatively few studies on the disposition properties of quinidine. We have studied in 10 normal subjects conventional quinidine sulfate and a slow-release quinidine bisulfate. Single and repetitive doses were given; blood and urine concentrations were measured by the method of Cramer and Isaakson.⁵ After a single dose of two tablets of quinidine sulfate (400 mg), the average peak concentration was 2.13 ± 0.22 μg/ml (±SEM); following two tablets of the slow-release form, the average peak concentration was 1.17 ± 0.12 μg/ml. T-_max was approximately 2 hr with quinidine sulfate and 4 hr with quinidine bisulfate. One fourth of both forms of the drug was recovered in the urine. Total body clearance was 0.36 L/kg hr and renal clearance was 117 ± 22 mllmin for both. With multiple dosing the serum quinidine concentration was higher than these predicted from the results of the single-dose study. Based on the mean estimates of quinidine half-life of 6 hr, a rapid method for achieving steady-state levels of quinidine would be to give an initial dose twice that of the maintenance dose. With the slow-release product if an equivalent dose was given every 12 hr, the mean steady-state quinidine serum concentration would be approximately the same.