Clinical Pharmacokinetics of N-acetylprocainamide
Clinical Pharmacokinetics of N-acetylprocainamide
复制标题
N-乙酰普鲁卡因酰胺的临床药代动力学
作者：
S. Connolly;R. Kates
由于在接受普鲁卡因胺治疗的患者的尿液中发现了N-乙酰普鲁卡因胺，因此已将该化合物作为普鲁卡因胺的代谢物和单独的抗肿瘤剂进行了研究。口服给药后，N-乙酰普鲁卡因胺的吸收超过80%。在肾功能正常的受试者中，59 - 89%的N-乙酰普鲁卡因胺以原型经尿液排泄。N-乙酰普鲁卡因胺脱乙酰化为普鲁卡因胺是N-乙酰普鲁卡因胺消除的次要途径。据报道，在肾功能正常的患者中，N-乙酰普鲁卡因胺的半衰期为4.3至15.1小时。据报告，肾功能正常患者中N-乙酰普鲁卡因胺的总体清除率（平均值± SD）范围为2.08 ± 0.36 ml/min/kg至3.28 ± 0.52 ml/min/kg。N-乙酰普鲁卡因胺清除率与肌酐清除率之间存在线性关系。N-乙酰普鲁卡因胺在功能性无肾患者中的半衰期可能长达42小时：然而，它可以通过血液透析从血浆中有效清除。N-乙酰普鲁卡因酰胺与蛋白质结合率为10%。N-乙酰普鲁卡因胺清除率存在年龄相关性下降，主要是由于随着年龄的增长肌酐清除率下降。在新生儿中，N-乙酰普鲁卡因酰胺的半衰期延长。几个治疗试验进行了评估N-乙酰普鲁卡因胺在抑制慢性室性早搏的有效性，现在已经报道。如果对N-乙酰普鲁卡因胺有治疗反应，则可能在血浆浓度为15 - 25μg/ml时发生。据报道，与药物抑制相关的浓度范围与无法耐受的副作用开始发生的浓度范围之间存在高度重叠。尽管血浆浓度高达40μg/ml，但口服治疗未报告重度心脏毒性。然而，据报道，低血压与快速静脉推注N-乙酰普鲁卡因胺有关。已推荐最大静脉输注速率为50 mg/min。N-乙酰普鲁卡因胺在接受普鲁卡因胺治疗的患者中：然而，在肾功能正常的患者中，N-乙酰普鲁卡因胺浓度仍低于治疗范围。在接受普鲁卡因胺治疗的肾衰竭患者中，N-乙酰普鲁卡因胺浓度急剧升高。肾功能不全患者必须调整N-乙酰普鲁卡因胺的剂量，对于高龄和低龄患者应更加谨慎使用。在接受N-乙酰普鲁卡因胺或普鲁卡因胺治疗的肾功能不全患者中，以及在非常年轻和老年患者中，N-乙酰普鲁卡因胺血浆浓度监测将具有临床价值。
SummarySince N-acetylprocainamide was identified in the urine of patients receiving procainamide, this compound has been studied both as a metabolite of procainamide and as a separate antiarrhythmic agent. N-acetylprocainamide absorption following oral administration is more than 80% complete. 59 to 89% of N-acetylprocainamide is excreted unchanged in the urine in subjects with normal renal function. Deacetylation of N-acetylprocainamide to procainamide is a minor route of N-acetylprocainamide elimination.The half-life of N-acetylprocainamide in patients with normal renal function has been reported to vary between 4.3 and 15.1 hours. Total body clearance (mean ± SD) of N-acetylprocainamide in patients with normal renal function has been reported to range from 2.08 ± 0.36ml/min/kg to 3.28 ± 0.52ml/min/kg. There is a linear relationship between N-acetylprocainamide clearance and creatinine clearance. The half-life of N-acetylprocainamide in functionally anephric patients may be as long as 42 hours: however, it can be effectively cleared from plasma by haemodialysis. N-acetylprocainamide is 10% protein-bound. There is an age-related decline in N-acetylprocainamide clearance, mostly due to the decrease in creatinine clearance that occurs with ageing. In the neonate, the half-life of N-acetylprocainamide is prolonged. Several therapeutic trials carried out to assess the effectiveness of N-acetylprocainamide in suppressing chronic ventricular premature beats have now been reported. If there is a therapeutic response to N-acetylprocainamide it will probably occur at a plasma concentration between 15 and 25μg/ml. A high degree of overlap has been reported between the concentration range associated with arrhythmic suppression and the range of concentrations where intolerable side effects begin to occur. No severe cardiac toxicity has been reported with oral therapy despite plasma concentrations as high as 40μg/ml. However, hypotension has been reported in association with a rapid intravenous bolus of N-acetylprocainamide. A maximum intravenous infusion rate of 50mg/min has been recommended.N-acetylprocainamide in patients receiving procainamide: however, N-acetylprocainamide concentrations remain below the therapeutic range in patients with normal renal function. In patients with renal failure receiving procainamide, N-acetylprocainamide concentrations rise dramatically.The dose of N-acetylprocainamide must be adjusted in patients with renal insufficiency, and it should be used more cautiously in the very old and very young. N-acetylprocainamide plasma concentration monitoring would be valuable clinically in patients with renal insufficiency receiving either N-acetylprocainamide or procainamide, and in the very young and the aged.