Practical pharmacokinetics of ventricular antiarrhythmic therapy

An increasing number of antiarrhythmic agents have become available for the treatment of ventricular tachyarrhythmias. Appropriate application of pharmacokinetic principles is essential to determine dosage amount and frequency, particularly because of the life-threatening consequences of inadequate therapy. Therefore absorption, distribution, metabolism, and elimination of antiarrhythmic agents must be considered in their use. Although some may be given intramuscularly, antiarrhythmic drugs are usually administered either intravenously for rapid onset of action or orally during long-term therapy. Distribution of antiarrhythmic drugs may be influenced by physicochemical properties of the drug (i.e., protein binding) or by tissue blood flow. Drug interactions and half-life are also important considerations. Finally, the major routes of elimination of antiarrhythmics are hepatic metabolism and renal and biliary excretion. The pharmacokinetic profiles of drugs used for the treatment of ventricular tachyarrhythmia, all of which are types I and III antiarrhythmic agents, are discussed.