Disopyramide: clinical indications, pharmacokinetics and laboratory assessment

Disopyram ide is an antiarrhythm ic drug similar to quinidine and used prim arily 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, cardiovas­ cular problems, and some gastrointestinal discomfort. Disopyramide is metabolized to N-desisopropyl disopyramide in the liver with approxi­ mately 50 percen t of the parent drug excreted unchanged. The elim ina­ tion 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 extrem ely variable degree of protein b inding (10 to 70 percent), which is highly dependen t on concentration. The unbound (free) fraction increases with increasing drug concentration, making the interpretation of total disopyra­ m ide concentrations very difficult. Since the free drug concentration is more representative of availability to its receptor, and only the free frac­ tion is available for renal excretion, the free drug concentration may rep ­ resen t a b e tte r predictor of therapeutic effectiveness. M ethods for d e te r­ mining concentrations of disopyramide include gas chromatography, high perform ance liquid chromatography, homogeneous enzyme immunoassay (EMIT), and fluorescence polarization immunoassay. A m ethod for p e r­ forming both total and free disopyramide determ inations is also described.