Disposition kinetics of disopyramide in patients with renal insufficiency

The pharmacokinetics of an intravenous injection of disopyramide was studied in five normal subjects and six patients with varying degrees of renal impairment. The elimination rate constant (beta) was related to the endogenous creatinine clearance (Clcr). However, a decrease in beta was not observed until the Clcr was reduced below 40 ml min-1. Below 40 ml min-1 a linear relationship existed between beta and Clcr. Similarly, the plasma elimination half-life (t 1/2 beta) showed a significant increase when the Clcr was less than 30 ml min-1. Hence, dosage modification for disopyramide is necessary only when renal function is severely impaired. Overall, the apparent volume of distribution in patients with renal insufficiency was reduced to two-thirds of that in normal subjects. Therefore, in patients with Clcr less than 40 ml min-1 both the loading and maintenance dose of disopyramide should be reduced.