Clinical value of plasma concentrations of antiarrhythmic drugs.

The clinical use of plasma concentrations of antiarrhythmic agents suffers from important limitations. Any factor changing the protein binding capacity affects the free, clinically active, fraction of the drug. Most antiarrhythmic agents attach to the acute phase alpha-1-acid glycoprotein, varying during conditions such as acute myocardial infarction, leading to changes in the plasma binding capacity for e.g. lidocaine. Several pharmacodynamic factors may counteract or potentiate the electrophysiological or haemodynamic action of antiarrhythmic agents. Active metabolites contribute to the clinical efficacy or to the side-effects. The induction of metabolizing enzymes of some drugs and the inhibition of hepatic metabolism of others may change the free drug fraction in plasma. While many studies show a good correlation between plasma levels and antiarrhythmic effect, few imply a correlation between plasma levels and a decrease in mortality. However, in spite of these limitations, plasma levels may be useful in guiding treatment with high dosages, with drugs with long elimination half-lives, in treatment failures due to true failure of the drug, changes in pharmacokinetics or because of poor patient compliance, and may be of particular interest when side-effects and/or intoxication are suspected.