Disopyramide: clinical indications, pharmacokinetics and laboratory assessment

Disopyramide is an antiarrhythmic drug similar to quinidine and used primarily to treat ventricular ectopic systoles. Unlike quinidine which shows drug-drug interaction with digoxin, disopyramide appears to be free of this problem. Side effects include anticholinergic symptoms, cardiovascular problems, and some gastrointestinal discomfort. Disopyramide is metabolized to N-desisopropyl disopyramide in the liver with approximately 50 percent of the parent drug excreted unchanged. The elimination half-life varies from 4.5 to nine hours, and it can be even longer in cases of renal failure or myocardial infarction. There exists an extremely variable degree of protein binding (10 to 70 percent), which is highly dependent on concentration. The unbound (free) fraction increases with increasing drug concentration, making the interpretation of total disopyramide concentrations very difficult. Since the free drug concentration is more representative of availability to its receptor, and only the free fraction is available for renal excretion, the free drug concentration may represent a better predictor of therapeutic effectiveness. Methods for determining concentrations of disopyramide include gas chromatography, high performance liquid chromatography, homogeneous enzyme immunoassay (EMIT), and fluorescence polarization immunoassay. A method for performing both total and free disopyramide determinations is also described.