Tuininga Y S, Crijns H J, Oosterhuis B, Wiesfeld A C, van Wijk L M, Albronda F, de Bruin H, Jonkman J H, Kozma C, Lie K I
Department of Cardiology, University Hospital, Groningen, The Netherlands.
J Cardiovasc Pharmacol. 1994 Mar;23(3):408-14.
The hemodynamic and pharmacokinetic effects of the novel class 1c antiarrhythmic drug restacorin were investigated in two groups of patients. Group I consisted of 5 patients with normal left ventricular (LV) function, and group II consisted of 10 patients with mild heart failure [New York Heart Association (NYHA) II; mean LV ejection fraction 33 +/- 6%]. The study had an open label, baseline-controlled, single-dose design. Restacorin was infused in a total dosage of 1.2 mg/kg. In group I, the only significant change as compared with baseline findings was a 25% increase in right atrial pressure. In group II; cardiac output (CO), dP/dt, and stroke work index (SWI) decreased significantly (-18, -11, and -24%, respectively). In addition, a significant 32% increase was noted in pulmonary artery wedge pressure (PAWP), and a 27% increase occurred in systemic vascular resistance (SVR). No changes were observed in heart rate (HR) or mean arterial blood pressure (MAP). CO and SVR at baseline correlated with the average plasma concentrations (r = -0.65 and p = 0.009 and r = 0.56 and p = 0.028 respectively). Creatinine clearance was inversely correlated to the restacorin plasma concentration (r = -0.51, p = 0.05). The half-life (t1/2) elimination time of restacorin was 2.60 h for group I, and 4.06 h for group II. Clearance was 51.4 and 32.2 L.h-1, respectively. Restacorin appears to be well tolerated in patients with normal LV function. The drug is not recommended for use in patients with reduced LV function because of its moderate negative inotropic effect.
在两组患者中研究了新型1c类抗心律失常药物瑞斯塔可林的血流动力学和药代动力学效应。第一组由5名左心室（LV）功能正常的患者组成，第二组由10名轻度心力衰竭患者组成[纽约心脏协会（NYHA）II级；平均左心室射血分数33±6%]。该研究采用开放标签、基线对照、单剂量设计。瑞斯塔可林的总输注剂量为1.2mg/kg。在第一组中，与基线结果相比，唯一显著的变化是右心房压力增加了25%。在第二组中，心输出量（CO）、dp/dt和每搏功指数（SWI）显著降低（分别降低了18%、11%和24%）。此外，肺动脉楔压（PAWP）显著增加了32%，全身血管阻力（SVR）增加了27%。心率（HR）或平均动脉血压（MAP）未见变化。基线时的CO和SVR与平均血浆浓度相关（r分别为-0.65和p=0.009以及r=0.56和p=0.028）。肌酐清除率与瑞斯塔可林血浆浓度呈负相关（r=-0.51，p=0.05）。瑞斯塔可林在第一组的半衰期（t1/2）消除时间为2.60小时，在第二组为4.06小时。清除率分别为51.4和32.2L·h-1。瑞斯塔可林在左心室功能正常的患者中似乎耐受性良好。由于其具有中度负性肌力作用，不建议在左心室功能减退的患者中使用该药物。
