Relative absorption of disopyramide as determined by liquid chromatography following acute administration of standard...

The absorption of disopyramide has been studied in healthy volunteers following an acute dose of 300 mg in standard capsules (C) and three controlled-release (CR) tablets with different in vitro release rates. Plasma concentrations and the urinary excretion of unchanged compound and its main metabolite, N-deisopropyldisopyramide, were determined simultaneously by using a rapid and sensitive method based on liquid-solid chromatography. The rate of absorption was rapid following C, and maximal concentrations were reached within 1.5-2 h. A CR formulation produced a slower rate of absorption and the rate correlated with the drug in vitro release rate. The maximal concentration of disopyramide was reduced following CR tablets. The extent of absorption was the same following C and two of the CR formulations, whereas the CR composition with the slowest in vitro release rate presented a somewhat reduced extent of absorption. About 70% of the given dose was recovered in urine as disopyramide (50%) and metabolite (20%). The elimination half-life of disopyramide and N-deisopropyldisopyramide was close to 4 and 7 h, respectively.