Gastrointestinal dialysis of disopyramide in healthy subjects

The effect of oral activated charcoal on the clearance of disopyramide was investigated in six healthy subjects. Oral administration of multiple doses of activated charcoal at 4, 6, 8 and 12 h after ingestion of the drug reduced the serum levels of both disopyramide and its main metabolite, mono-N-dealkyldisopyramide (MND). The mean serum level of disopyramide at 24 h after oral administration of the drug was significantly decreased from 0.22 in the control to 0.091 micrograms/ml by multiple doses of activated charcoal. The serum half-life and AUC0-infinity were decreased to 67% and 81%, respectively, and the apparent total body clearance was increased to 122% as compared with the control treatment. The apparent volume of distribution was not significantly different between both treatments. The cumulative amounts of urinary excretion of both disopyramide and MND with activated charcoal treatment were decreased as compared with those in the control treatment. Mean residence time (MRT) of disopyramide obtained from the serum data decreased from 7.8 (control) to 6.9 h (charcoal treatment) and the values were approximately consistent with those obtained from the urinary data. These results indicate that oral administration of activated charcoal would enhance the clearance of disopyramide in acute drug poisoning even after the drug has been absorbed into the systemic circulation from the g.i. tract.