Shaw L M, Doherty J U, Waxman H L, Josephson M E
Angiology. 1987 Feb;38(2 Pt 2):192-7.
We have evaluated the influence of several factors on the binding of disopyramide to protein in human serum using a new ultrafiltration system and the enzyme multiplied immunoassay technique (EMIT) for disopyramide immunoassay. From these studies and those of other investigators, we conclude that the most significant in vivo factors influencing disopyramide binding in human serum are total disopyramide concentration, the concentration of alpha 1-acid glycoprotein, and the concentration of mono-N-dealkyldisopyramide. Significant variation in binding occurs in patients whose total disopyramide concentration is within the therapeutic range. The proportion of free disopyramide ranged from 16% to 54% in the sera of 50 cardiac patients whose total disopyramide concentration ranged from 0.5 to 5.8 mcg/ml. Since there is so much variation in the proportion of disopyramide that is free, and since it is the unbound form of the drug that is pharmacologically active, it is likely in patients whose arrhythmia responds to disopyramide therapy that unbound drug concentration will be a better indicator of drug efficacy and toxicity than will be total drug concentration. To test this hypothesis, we are investigating the relationship between steady state total and unbound disopyramide plasma levels in patients with supraventricular or ventricular arrhythmias, and pharmacologic response as determined by standard intracardiac electrophysiologic studies.
我们使用一种新的超滤系统和用于丙吡胺免疫测定的酶倍增免疫测定技术（EMIT），评估了几种因素对丙吡胺与人血清中蛋白质结合的影响。从这些研究以及其他研究者的研究中，我们得出结论，影响人血清中丙吡胺结合的最重要的体内因素是丙吡胺总浓度、α1-酸性糖蛋白浓度和单-N-去烷基丙吡胺浓度。在丙吡胺总浓度处于治疗范围内的患者中，结合存在显著差异。在50名心脏病患者的血清中，丙吡胺总浓度范围为0.5至5.8 mcg/ml，游离丙吡胺的比例在16%至54%之间。由于游离丙吡胺的比例存在如此大的差异，并且由于药物的未结合形式具有药理活性，对于心律失常对丙吡胺治疗有反应的患者，未结合药物浓度可能比总药物浓度更能准确反映药物疗效和毒性。为了验证这一假设，我们正在研究室上性或室性心律失常患者的稳态丙吡胺血浆总水平和未结合水平之间的关系，以及通过标准心内电生理研究确定的药理反应。
