Effect of phenytoin on serum disopyramide concentrations

The effects of phenytoin on serum disopyramide concentrations in 10 volunteers were studied. Leading to the study was the case of a 59-year-old man who received phenytoin and disopyramide and who required unusually high doses of disopyramide and an unusually high serum concentration of this drug to control his ventricular tachycardia. Ten healthy men 23-36 years of age each received a single oral dose of disopyramide phosphate 300 mg. Periodic blood samples were obtained for 24 hours after the dose. On day 2, the subjects began a 13-day course of oral phenytoin sodium 300 mg/day, and on day 14 each again received a single oral dose of disopyramide, after which blood samples were obtained. Serum disopyramide concentrations were determined by enzyme-mediated immunoassay and gas chromatography and serum phenytoin concentrations by fluorescence polarization immunoassay. Pharmacokinetic values before and after phenytoin administration were calculated. The mean area under the serum concentration-time curve for disopyramide and the disopyramide half-life and elimination rate constant were significantly different before and after phenytoin treatment. The maximum serum disopyramide concentrations were not significantly different. After phenytoin therapy, subjective complaints of anticholinergic effects increased in number and severity. An interaction between disopyramide and phenytoin appears to exist and to be caused by an increase in the hepatic metabolism of disopyramide.(ABSTRACT TRUNCATED AT 250 WORDS)