Plasma level monitoring of antiarrhythmic drugs

It is widely accepted that the effects (both cardiac and extracardiac) of antiarrhythmic drugs are modulated by their concentration at some unidentified active site, and that the drug concentrations in the systemic circulation and at these active sites are in equilibrium. Thus, antiarrhythmic drug effects can be related directly to systemic plasma concentrations, and an optimal plasma concentration can be identified at which satisfactory arrhythmia suppression can be achieved in the absence of intolerable adverse effects. This optimal concentration is influenced by several factors that give rise to significant interpatient variability. These factors include serum protein binding, active metabolites, intrinsic responsiveness and myocardial accumulation. Although plasma concentration guidelines have been suggested for most antiarrhythmic drugs, they are generally not statistically derived and, with the exception of procainamide, are extrapolated from small patient samples. They generally represent the experience of an investigator or group of investigators treating a small homogeneous patient population. Interpretation of plasma concentrations of antiarrhythmic drugs also requires consideration of pharmacokinetic factors. Plasma drug levels are only useful when dosing history and timing of the blood sample, relative to drug administration, are considered. Despite several limitations, plasma concentration monitoring of antiarrhythmic drugs can be helpful if evaluated with an understanding of the pharmacokinetic properties of the drug being measured, the clinical status of the patient and an appreciation of the factors that may influence the relation between the measured level and resultant clinical response.