Kessler K M, Kissane B, Cassidy J, Pefkaros K C, Kozlovskis P, Hamburg C, Myerburg R J
Circulation. 1984 Sep;70(3):472-8. doi: 10.1161/01.cir.70.3.472.
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.
急性心肌梗死期间游离脂肪酸和α1-糖蛋白浓度的变化，会对某些药物的血清蛋白结合产生异步且相反的影响。在20例急性心肌梗死患者中，研究了具有不同结合特性的两种抗心律失常药物（奎尼丁和普鲁卡因胺）的游离药物分数与第1至5天以及第10天游离脂肪酸和α1-糖蛋白浓度之间的关系。奎尼丁的平均游离分数在第1天升高（稳定心脏病患者为9.0±4.4%，而稳定心脏病患者为6.7±2.7%；p<0.05），并随着游离脂肪酸浓度降低（第1天=464±272毫当量/升；第10天=264±155毫当量/升；p<0.01）和α1-糖蛋白浓度升高（第1天=98±31毫克/分升；第10天=141±47毫克/分升；p<0.02）而逐渐下降至第10天（4.0±2.8%；p<0.0002）。多元逐步回归显示，α1-糖蛋白浓度的变化对观察到的游离奎尼丁分数的顺序变化有主要影响（p<0.005）。相比之下，未观察到普鲁卡因胺结合的系列变化。总之，急性心肌梗死过程中的代谢变化会依次改变游离奎尼丁分数，从而可能影响药效学。
