The myocardial levels of the antiarrhythmic drugs: clinical relevance.

Valuable knowledge has been recently achieved in the field of pharmacokinetics of antiarrhythmics, but few data are still available about myocardial concentrations attainable by such drugs, especially as far as the clinical implications of the binding mechanisms and the relationships with plasma levels are concerned. According to the "modulated receptor theory", not only beta-blockers or verapamil but also class I agents should act by a receptor mechanism. In general, antiarrhythmics attain myocardial levels largely higher than the plasmatic concentrations and the non-specific binding greatly exceeds the specific one. Moreover, some relevant causes of lack of correlation between plasma levels and drug response (such as active metabolites, acid-base or ionic disorders, ischemia, receptor changes etc.) are not removed by the determination of myocardial level, which is quite unpractical and does not offer clear advantages in comparison to the conventional plasma monitoring.