Comparative quinidine plasma profiles at steady state of two controlled-release products and quinidine sulfate in...

A study was conducted to compare, at steady state, the plasma quinidine level profiles of two commercial controlled-release products (quinidine sulfate controlled release and quinidine gluconate controlled release) with quinidine sulfate given in solution. Twenty-four healthy volunteers entered the study and 23 completed it. Quinidine formulations were given at 600 mg day-1 for 4 days in each of three periods in a randomized crossover study. In addition to frequent blood sampling on the fourth day of each period, samples were taken during the approach to steady state to confirm by minimum plasma concentrations (Cmin) that steady state had been attained. Quinidine concentrations were measured by using a high-performance liquid chromatographic assay specific for quinidine. The bioavailability of the two controlled-release products relative to quinidine sulfate in solution was adequate when dose correction to account for differences in quinidine base content was done. Without dose correction, the area under the plasma concentration-time curve (AUC) for the quinidine gluconate form was 85 per cent that of the solution: an amount equivalent to the relative actual amount of quinidine base in the quinidine gluconate dosage form. The maximum plasma concentration (Cmax), Cmin, peak-to-trough differences, and AUC from the quinidine sulfate extended-release form given 300 mg q12h were similar to the solution given 150 mg q6h. With dose correction, the quinidine gluconate controlled-release form given q12h had equivalent AUC but larger peak-to-trough differences than either the quinidine sulfate extended-release product given q12h or quinidine sulfate in solution given q6h.