Dynamic variability of binding of antiarrhythmic drugs during the evolution of acute myocardial infarction.
We tested the hypothesis that the changes in free fatty acid and alpha 1-glycoprotein concentrations, which occur during acute myocardial infarction, exert asynchronous and opposing influences on the serum protein binding of selected drugs. Free drug fractions of two antiarrhythmic agents with contrasting binding characteristics, quinidine and procainamide, were related to free fatty acid and alpha 1-glycoprotein concentrations on days 1 through 5 and 10 in 20 patients with acute myocardial infarction. The mean free quinidine fraction was elevated on day 1 (9.0 +/- 4.4% vs 6.7 +/- 2.7% in patients with stable heart disease; p less than .05) and fell progressively to day 10 (4.0 +/- 2.8%; p less than .0002) as free fatty acid concentration decreased (day 1 = 464 +/- 272 meq/liter; day 10 = 264 +/- 155 meq/liter; p less than .01) and alpha 1-glycoprotein concentration increased (day 1 = 98 +/- 31 mg/dl; day 10 = 141 +/- 47 mg/dl; p less than .02). Multiple stepwise regression showed a major influence of changing alpha 1-glycoprotein concentration on the observed sequential changes in the free quinidine fraction (p less than .005). In contrast, no serial changes in procainamide binding were noted. In conclusion, metabolic changes during the course of acute myocardial infarction sequentially alter free quinidine fraction and, consequently, may influence pharmacodynamics.
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000097:blood*; D009961:Orosomucoid / Q000032:analysis; D011342:Procainamide / Q000097:blood; D011485:Protein Binding; D011802:Quinidine / Q000097:blood
D000889:Anti-Arrhythmia Agents; D001798:Blood Proteins; D005230:Fatty Acids, Nonesterified; D006023:Glycoproteins; D009961:Orosomucoid; D011802:Quinidine; D011342:Procainamide