Pharmacokinetics and optimum dose of disopyramide in patients with chronic renal failure

The pharmacokinetics and optimum dose for maintenance of disopyramide (DP) which is effective against arrhythmia were studied in patients with chronic renal failure (CRF, n = 10), who had a creatinine clearance (Ccr) less than 30 ml/min. The plasma concentrations (PC) of DP and mono-isopropyl-disopyramide (MDP) an active metabolite of DP, were measured by high performance liquid chromatography. Samples from patients and controls were obtained at 0, 1, 2, 3, 4, 6, 8, 12, 24, 33, and 48 hr after oral administration (OA) of 100 mg DP. The pharmacokinetic parameters were calculated using a two-compartment model. In CRF, the plasma half life (T 1/2) of DP was 5.25 to 22.42 hr (average is 12.45 hr) and that of MDP was 5.09 to 131.66 hr (average is 16.9 hr). In normal controls, the T 1/2 of DP was 6.05 hr, but that of MDP could not be determined the available sensitivity of measurement. T max was 3.11 hr at the total PC of DP and MDP, and C max was 2.48 g/ml on average. In conclusion, the present study revealed that: (1) the PC of a mixture of DP and MDP should rise following OA of DP every 8 or 12 hr in CRF; (2) it is necessary therefore to monitor the accumulation of MDP after rolling OA of DP; and (3) OA of DP every 24 hr can maintain an effective PC.