The acute changes in serum binding of disopyramide and flecainide after myocardial infarction.
In the serum basic drugs are principally bound to alpha1-acid glycoprotein (AAG). Following acute myocardial infarction it has been shown that the levels of AAG rise. The serum levels of total protein, albumin, AAG and the protein binding of 2 antiarrhythmic drugs which are bases, disopyramide and flecainide, was measured in vitro with blood samples from eleven patients taken over the first 5 days following myocardial infarction. Mean AAG levels significantly increased from 1.04 g/l on Day 1 to 1.80 g/l on Day 5. The binding of disopyramide, which is highly bound, rose from 80% to 87%, representing a 35% decrease in free drug concentration. In contrast the binding of flecainide fell from 61% to 53%, a 20% increase in free drug concentration. These data suggest that although the binding of strongly bound drugs responds appropriately to increases in binding protein after acute myocardial infarction, poorly bound drugs are displaced from binding sites possibly by endogenous substances. Since the pharmacological effects of a drug are related to its free (unbound) concentration, the changes in the proportions of free to bound drug after myocardial infarction may have important clinical implications.
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D004206:Disopyramide / Q000097:blood*; D005260:Female; D005424:Flecainide; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D009961:Orosomucoid / Q000378:metabolism; D010880:Piperidines / Q000097:blood*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D001798:Blood Proteins; D009961:Orosomucoid; D010880:Piperidines; D012709:Serum Albumin; D004206:Disopyramide; D005424:Flecainide