Stereoselective gastrointestinal clearance of disopyramide in rabbits treated with activated charcoal

The ability of activated charcoal to enhance the drug elimination of two enantiomers, R- and S-disopyramide, was compared in rabbits. Orally administered activated charcoal significantly decreased the area under the serum concentration curve of R-disopyramide, whereas the same treatment had no effect on that of S-disopyramide. The difference could be explained by the difference in the hepatic extraction ratio of two enantiomers in rabbits. S-Disopyramide is a drug of high hepatic extraction ratio in rabbits and R-disopyramide is of intermediate hepatic extraction ratio. Equations were derived to illustrate the influence of the hepatic extraction ratio on the apparent gastrointestinal clearance. A higher hepatic extraction ratio decreases the apparent gastrointestinal clearance of a drug. This phenomenon may explain some unsuccessful experiments of gastrointestinal dialysis. When considering the use of activated charcoal to enhance systemic drug elimination, the hepatic extraction ratio of the drug should be included.