Serum disopyramide concentrations and suppression of ventricular premature contractions

Abstract

Serum disopyramide determinations and 24-hour Holter monitoring were performed in 20 cardiac subjects with ventricular premature contractions (VPCs) after the first, seventeenth, and thirty-seventh doses of disopyramide, 100 mg (10 subjects; low-dose group) or 200 mg (10 subjects; high-dose group) every 6 hr for 10 days to assess the ability of single- or first-dose data to predict serum disopyramide concentrations at steady state and the relationship between steady-state serum disopyramide concentrations and VPC suppression. Control Holter recordings were made for 48 hr in each subject. There were strong correlations in both groups between data for the AUC over 0 to 6 hr for the first dose (AUC60) and average (C ss) and trough (C min) steady-rate serum disopyramide concentrations after the seventeenth and thirty-seventh doses and the two combined. C ss and C min were related to AUC60 by the following expressions for both dosage groups: C ss = 0.22 AUC60 + 0.90 and C min = 0.20 AUC60 + 0.70. There were good correlations between 6-hr serum disopyramide concentration after the first dose and C ss and C min. There was strong correlation between overall average steady-state serum disopyramide concentration and suppression of VPC frequency. The relationship between VPC suppression and overall average trough serum disopyramide concentration at steady state, on the other hand, was weak.

Free Drug Concentration Monitoring in Clinical Practice

“…MND has been shown to have minimal effect against ventricular arrhythmias compared with disopyramide (Chiang et al 1985;Karim et al 1982), although in severe renal failure accumulation of MND may give rise to pharmacologically important concentrations. More recent work in patients and volunteers has shown that total concentration of disopyramide is correlated with changes in QTc (Bryson et al 1978;Chiang et al 1985;Hinderling & Garrett 1976;Whiting et al 1980) and the reduction in the frequency of ventricular ectopic beats (Ueda et al 1984). Thus, monitoring of total disopyramide concentration to optimise pharmacological effect is supported by experimental data from humans.…”

Kinetics of Disopyramide after Intravenous Infusion to Patients with Myocardial Infarction and Heart Failure

“…From a clinical point of view the intravenous dose regimen suggested by Deano et al (1977) and used in the present study is acceptable in patients with myocardial infarction and heart failure. Ueda et al (1984) found a correlation between steady state serum concentration of disopyramide and the suppression at VPC, while no correlation could be demonstrated between the effect of disopyramide and the minimal concentration during continuous oral administration. Patients not responding, however, were excluded from the correlation analysis, and in our experience monitoring of total serum concentration of disopyramide is of only limited value.…”

Disopyramide concentrations in human plasma and saliva: Comparison of disopyramide concentrations in saliva and plasma unbound concentrations

“…It is reported that the effective therapeutic concentration in plasma of disopyramide is between 2 and 4 g · ml )1 [4], and that over 5.5 g · ml )1 the occurrence frequency of adverse effects becomes larger [5]. It is also recognized that disopyramide is one of the drugs which inter-individual variations among patients for pharmacokinetic parameters and therapeutic effects are very large [6,7]. Therapeutic drug monitoring (TDM) is important for the drugs which have a narrow therapeutic range and a large variation in plasma drug concentrations among patients.…”