Disopyramide kinetics in renal impairment: determinants of interindividual variability

Disopyramide kinetics were studied in 30 patients with normal to severely impaired renal function (endogenous creatinine clearance 7.6 to 116.9 ml/min/1.73 m2) after intravenous bolus injection. Serum concentration-time curves were fitted to an open two-compartment model. There was close correlation between renal disopyramide clearance and creatinine clearance (r = 0.922). Disopyramide body clearance or elimination rate constant (kel beta) and creatinine clearance did not correlate as closely (r = 0.756 and 0.644). Volume of distribution at steady state and extrarenal clearance of disopyramide both correlated slightly positively with renal function. Disopyramide body clearance and volume of distribution, but not kel beta, were found to be dose dependent. Disopyramide kinetics in renal impairment were not sufficiently predictable from clinical data of the patient because of great interindividual variation in drug disposition and renal and extrarenal elimination. Dosage regimen must therefore be based on individual response and controlled by the clinical effect and estimates of disopyramide serum concentration.