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Tocainide kinetics in congestive heart failure
Abstract:
Our subjects were 20 patients with life-threatening or symptomatic ventricular arrhythmias refractory to standard oral antiarrhythmic drugs but responsive to intravenous lidocaine. After evaluation of arrhythmias and treatment with intravenous lidocaine, oral tocainide dosage regimens were based on age, weight, and clinical status. During initial tocainide treatment, six plasma tocainide concentrations were recorded within a single dosing interval in 17 of 20 patients, by which standard kinetic parameters were calculated. Eventual trough steady-state tocainide plasma concentrations were predicted from the derived patient-specific kinetic parameters. Mean daily tocainide dose was 1800 mg (1200 to 2400). Mean daily tocainide doses (milligram per kilogram) did not differ significantly among responders and nonresponders or among patients with or without congestive heart failure. Mean peak and trough plasma concentrations 48 hr after initiation of therapy were 9.8 and 7.5 mcg/ml. Tocainide plasma concentrations did not correlate with responders and nonresponders or identify patients who were developing adverse reactions to tocainide. There were no significant differences in any of the calculated kinetic parameters as a function of response to tocainide or the presence of congestive heart failure, but there was a trend toward smaller volumes of distribution and higher average plasma concentrations at steady state in patients with congestive heart failure. There were no significant kinetic differences among patients with and without congestive heart failure, but a trend toward higher plasma concentrations in patients with congestive heart failure and the small number of patients suggests that further data collection is necessary before dosage recommendations can be made.
Insights
Oral tocainide effectively treated ventricular arrhythmias in patients unresponsive to other drugs. However, tocainide plasma concentrations did not predict patient response or adverse reactions, necessitating further research for optimal dosing.
Area of Science:
- Pharmacology
- Cardiology
- Clinical Therapeutics
Background:
- Ventricular arrhythmias pose significant life-threatening risks.
- Standard oral antiarrhythmic drugs are not always effective.
- Intravenous lidocaine can be effective but is not suitable for long-term oral therapy.
Purpose of the Study:
- To evaluate the efficacy and pharmacokinetics of oral tocainide in patients with refractory ventricular arrhythmias.
- To determine if tocainide plasma concentrations correlate with therapeutic response or adverse events.
- To establish patient-specific kinetic parameters for predicting tocainide concentrations.
Main Methods:
- Twenty patients with refractory ventricular arrhythmias were treated with oral tocainide.
- Plasma tocainide concentrations were measured during initial therapy to calculate pharmacokinetic parameters.
- Steady-state concentrations were predicted using patient-specific kinetic data.
- Dosing regimens were adjusted based on age, weight, and clinical status.
Main Results:
- Oral tocainide was effective in managing ventricular arrhythmias.
- Mean daily tocainide dose was 1800 mg.
- Tocainide plasma concentrations did not correlate with response or adverse reactions.
- A trend towards higher plasma concentrations in patients with congestive heart failure was observed.
Conclusions:
- Oral tocainide is a viable treatment option for refractory ventricular arrhythmias.
- Current pharmacokinetic parameters and plasma concentrations do not reliably predict patient outcomes.
- Further studies are needed to refine tocainide dosing strategies, especially in patients with heart failure.