Prediction of acute myocardial disposition of antiarrhythmic drugs.
Using peripheral blood concentration and myocardial content data (from coronary sinus catheterization and serial determination of transmyocardial drug concentration gradients) from a previous clinical study of the antiarrhythmic drugs lidocaine and mexiletine, we tested the hypothesis that two prospectively defined models of myocardial drug disposition could be used to predict myocardial drug content, in the first 30 min following bolus iv injection, from peripheral blood concentrations alone. Compartmental analysis of peripheral blood concentration data from prolonged blood sampling (three-compartment model) and from the first 30 min after drug injection (two-compartment model) was used to calculate drug content, during the first 30 min, in the second compartment of each of the models. The time course of calculated compartmental content was similar to that of the measured myocardial content in 16 of the 18 patients studied, although there were some differences in the time of peak content. This relatively noninvasive method may therefore be useful in predicting the time course of myocardial drug content after acute iv drug administration.
Morgan
D J
DJ
Victorian College of Pharmacy, Melbourne, Australia.
Horowitz
J D
JD
Louis
W J
WJ
D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D006801:Humans; D008012:Lidocaine / Q000097:blood / Q000493:pharmacokinetics; D008801:Mexiletine / Q000097:blood / Q000493:pharmacokinetics; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D008012:Lidocaine