Population pharmacokinetics of intravenous amiodarone in patients with refractory ventricular tachycardia/fibrillation
Population pharmacokinetics of intravenous amiodarone in patients with refractory ventricular tachycardia/fibrillation
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DOI：
10.1002/j.1552-4604.1996.tb04240.x
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发表时间：
1996-08-01
影响因子：
2.9
通讯作者：
Chiang, ST
中科院分区：
文献类型：
--
作者：
KorthBradey, JM;Rose, GM;Chiang, ST
在245例接受静脉胺碘酮短期治疗难治性、血流动力学不稳定性、室性心动过速和/或室颤的患者中，采用群体方法确定胺碘酮的药代动力学。采用比例统计模型估计受试者间变异性的二室模型和估计残差的加性比例模型被发现最能描述数据。清除率的平均值（%变异系数，CV）为0.22 L/hr/kg（33%），中心分布容积为0.30 L/kg（11%），外周分布容积为10.0 L/kg（9.5%），房室间清除率为0.71 L/hr/kg（16%）。清除率的平均（%CV）受试者间方差估计值为1.52（31%），中央容量为0.37（46%），外周容量为0.37（67%），房室间清除率为0.44（39%）。残差估计值（%CV）为0.53（13%）。年龄、性别、身高、血清肌酐浓度、血清碱性磷酸酶活性、射血分数和对治疗的治疗反应对患者药代动力学的变异性没有影响，得出的结论是，这些患者中胺碘酮的药代动力学参数与健康志愿者报告的参数相似，并且具有相似的变异性，在短期观察期间进行的药代动力学参数估计值可能与接受单次给药的健康志愿者长期观察期间估计的参数不完全一致。
A population approach was used to determine the pharmacokinetics of amiodarone in 245 patients receiving intravenous amiodarone for the short-term treatment of refractory, hemodynamically destabilizing, ventricular tachycardia and/or fibrillation. A two-compartment model employing proportional statistical models to estimate intersubject variability and an additive-proportional model to estimate residual error were found to best describe the data. The mean (% coefficient of variation, CV) value for clearance was 0.22 L/hr/kg (33%), central volume of distribution was 0.30 L/kg (11%), peripheral volume of distribution was 10.0 L/kg (9.5%), and intercompartmental clearance was 0.71 L/hr/kg (16%). The mean (%CV) intersubject variance estimates were 1.52 (31%) for clearance, 0.37 (46%) for central volume, 0.37 (67%) for peripheral volume, and 0.44 (39%) for inter compartmental clearance. The estimate of residual error (%CV) was 0.53 (13%). Age, gender, height, serum creatinine concentration, serum alkaline phosphatase activity, ejection fraction, and therapeutic response to treatment did not contribute to the variability in patient pharmacokinetics, It was concluded that the pharmacokinetic parameters of amiodarone in these patients were similar to those reported for healthy volunteers and were similarly variable, Estimates of pharmacokinetic parameters made during short periods of observation may not be entirely consistent with parameters estimated during prolonged periods of observation of healthy volunteers who receive single doses.