Cameron J, Stafford W, Pritchard D, Norris R, Ravenscroft P
J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):126-31.
We studied the haemodynamic and pharmacokinetic effects of intravenous disopyramide phosphate in 12 patients (average age, 59 years) with proven transmural myocardial infarction, whose symptoms began less than 12 h prior to the study. The aim was to assess the effects of intravenous disopyramide (2 mg/kg given over 5 min) on cardiac index (CI), left ventricular filling pressure (LVFP), heart rate (HR), mean systemic arterial blood pressure (BP), and systemic vascular resistance (SVR) for 60 min after administration of the drug. Both total and free concentrations of disopyramide in the plasma were also measured. A significant elevation (p less than 0.01) of LVFP (estimated indirectly as pulmonary artery end-diastolic pressure) occurred and persisted through the 1-h evaluation period. There was a small but significant (p = 0.02) initial fall in CI and a rise in SVR (p = 0.05). No significant changes occurred in HR or BP. Serum concentrations of disopyramide reached recommended therapeutic concentrations. There was no significant correlation of the changes in cardiac variables from pretreatment values with total serum concentrations, but the free concentration of disopyramide in plasma correlated better with cardiac effect, and the relationships of the free concentration of disopyramide to the changes in LVFP and in SVR from pretreatment values were significant (p less than 0.05). In two patients studied in detail, there was evidence of dose-dependent protein binding of disopyramide.
我们研究了静脉注射磷酸丙吡胺对12例（平均年龄59岁）经证实为透壁性心肌梗死患者的血流动力学和药代动力学影响，这些患者的症状在研究开始前不到12小时出现。目的是评估静脉注射丙吡胺（5分钟内给予2mg/kg）给药后60分钟对心脏指数（CI）、左心室充盈压（LVFP）、心率（HR）、平均体循环动脉血压（BP）和体循环血管阻力（SVR）的影响。同时还测定了血浆中丙吡胺的总浓度和游离浓度。LVFP（间接估计为肺动脉舒张末期压力）显著升高（p<0.01），并在1小时评估期内持续存在。CI最初有小幅但显著（p=0.02）下降，SVR升高（p=0.05）。HR和BP无显著变化。丙吡胺的血清浓度达到推荐治疗浓度。心脏变量相对于治疗前值的变化与血清总浓度无显著相关性，但血浆中丙吡胺的游离浓度与心脏效应的相关性更好，丙吡胺游离浓度与LVFP和SVR相对于治疗前值变化的关系显著（p<0.05）。在详细研究的2例患者中，有证据表明丙吡胺存在剂量依赖性蛋白结合。
