Caplin J L, Johnston A, Hamer J, Camm A J
Eur J Clin Pharmacol. 1985;28(3):253-5. doi: 10.1007/BF00543319.
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.
在血清中，碱性药物主要与α1-酸性糖蛋白（AAG）结合。急性心肌梗死后，已表明AAG水平会升高。对11名患者在心肌梗死后的前5天采集的血样进行体外检测，测定了总蛋白、白蛋白、AAG的血清水平以及两种碱性抗心律失常药物（丙吡胺和氟卡尼）的蛋白结合情况。平均AAG水平从第1天的1.04 g/l显著增加至第5天的1.80 g/l。高度结合的丙吡胺的结合率从80%升至87%，这意味着游离药物浓度降低了35%。相比之下，氟卡尼的结合率从61%降至53%，游离药物浓度增加了20%。这些数据表明，虽然急性心肌梗死后强结合药物的结合会随着结合蛋白的增加而适当变化，但弱结合药物可能会被内源性物质从结合位点上置换下来。由于药物的药理作用与其游离（未结合）浓度相关，心肌梗死后游离药物与结合药物比例的变化可能具有重要的临床意义。
