N‐Acetylprocainamide Kinetics During Intravenous Infusions and Subsequent Oral Doses in Patients with Coronary Artery Disease and Ventricular Arrhythmias
N‐Acetylprocainamide Kinetics During Intravenous Infusions and Subsequent Oral Doses in Patients with Coronary Artery Disease and Ventricular Arrhythmias
复制标题
冠状动脉疾病和室性心律失常患者静脉输注和随后口服剂量期间的 N-乙酰普鲁卡因酰胺动力学
作者：
T. Ludden;M. Crawford;G. Kennedy
在5例冠状动脉疾病和室性心律失常患者（均为男性，平均年龄= 62岁）中研究了N-乙酰普鲁卡因胺（NAPA）在负荷输注0.22-0.45 mg/kg/min、延长（19-48小时）静脉输注2.5-5.2 mg/min期间的动力学，以及在其中4例患者中，在随后每8小时口服1.5-3 g剂量期间的动力学。通过高效液相色谱法测定NAPA的血清浓度。除一个例外情况外，个体浓度-时间曲线可通过具有表观一级消除的双室开放动力学模型描述。动力学变量为：初始分布容积（Vc）为0.20 ± 0.11 l/kg（平均值± SD）;稳态分布容积（Vss）为1.58 ± 0.55 l/kg;分布清除率（Cle）为133 ± 23 ml/（kg·hr）;吸收速率常数（Ka）为0.354 ± 0.173 hr−1;到达体循环的剂量分数（F）为1.00 ± 0.14。1例患者每8小时接受1. 5、2、2. 5和3 g递增口服剂量的数据导致在两个最高口服给药速率下观察到的浓度系统性预测不足。这表明NAPA的动力学行为可能存在一定程度的非线性或时间依赖性变化。在输注结束时仅发现低浓度的普鲁卡因胺，< 1 mg/L。
The kinetics of N‐acetylprocainamide (NAPA) were studied in 5 patients (all men, mean age = 62) with coronary artery disease and ventricular arrhythmias during loading infusions of 0.22–0.45 mg/kg/min, prolonged (19–48 hrs) intravenous infusions 2.5–5.2 mg/min, and in 4 of the patients, during subsequent oral doses 1.5–3 g every 8 hrs. Serum, concentrations of NAPA were determined by high‐performance liquid chromatography. The individual concentration‐time profiles could, with one exception, be described by a two‐compartment, open, kinetic model with apparent first‐order elimination. The kinetic variables were: initial distribution volume (Vc) 0.20 ± 0.11 l/kg (mean ± SD); steady‐state distribution volume (Vss) 1.58 ± 0.55 l/kg; distributional clearance (Cle) 133 ± 23 ml/(kg·hr); absorption rate constant (Ka) 0.354 ± 0.173 hr−1; and fraction of dose reaching systemic circulation (F) 1.00 ± 0.14. The data for one patient who had received increasing oral dosages of 1.5, 2, 2.5 and 3 g every 8 hours resulted in systematic underprediction of observed concentrations at the two highest oral dosing rates. This suggests the possibility of some degree of nonlinearity or time‐dependent change in the kinetic behavior of NAPA. Only low concentrations of procainamide, < 1 mg/L, were found at the end of the infusions.