Pharmacokinetics of disopyramide in patients with chronic renal failure

Abstract

The pharmacokinetics study of a single oral dose of 200 mg of disopyramide was performed in 22 normal control subjects and 33 patients with chronic renal failure (CRF). The latter were subdivided into 3 groups of 11 patients each as a function of the gravity of renal insufficiency. With the exception of maximum concentration (C max), which was only slightly modified, and of the apparent distribution volume which remained unchanged, all the other pharmacokinetic blood parameters (t max, concentration at 24th hour, elimination constant (ke h-1), elimination half-life, area under the curve and plasma clearance) were significantly modified in the CRF group; in particular, the elimination half-life was significantly increased (for 22 cases of CRF with mean plasma creatinine greater than 250 microM at 16.3 hours compared to 8.0 hours in controls). The urinary elimination of disopyramide was studied in 14 renal insufficiency patients and in 6 controls. The decreased rate of urinary excretion of disopyramide and its monodealkylated derivative (NMD), during the first 24 hours, was directly related to the severity of renal insufficiency. The ratio of urinary NMD/(disopyramide + NMD) was unchanged in CRF patients as compared to the controls. The results suggest that the dosage of disopyramide should be decreased when plasma creatinine values are greater than 250 microM, and creatinine clearance is less than 30 ml/min. The dose for a 70 kg subject would be 100 mg, administered every 12 hours.