Dose selection and population pharmacokinetics of PEG-Intron in patients with chronic myelogenous leukaemia
Dose selection and population pharmacokinetics of PEG-Intron in patients with chronic myelogenous leukaemia
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DOI：
10.1111/j.1365-2125.2006.02757.x
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发表时间：
2007-03-01
影响因子：
3.4
通讯作者：
Cutler, David
中科院分区：
文献类型：
--
作者：
Gupta, Samir;Jen, Juif;Cutler, David
目的：评价聚乙二醇化内含子-α 2b（PEG-Intron）在慢性粒细胞性白血病（CML）患者中的群体药代动力学剂量选择。方法：PEG-Intron 3-6 μ g kg（-1）皮下给药，每周一次，治疗48周后采集血样。从137名患者中收集的624份样本被纳入分析。使用非线性混合效应建模分析来自临床疗效试验的稀疏采样浓度数据。协变量包括体重、性别、年龄、种族、血清肌酐和估计肌酐清除率（CLcr）。治疗第4周的清除率为42.3 l天（-1）（CLcr 120 ml min（-1）的患者），患者间变异性30%。治疗第48周时，清除率值降至第4周值的69%。CLcr是根据体重、性别、年龄和血清肌酐计算的复合变量，对PEG-内含子的清除率有较小但具有统计学显著性的影响。结论PEG-Intron 6.0 μ g·kg ~（-1）·week ~（-1）治疗慢性粒细胞性白血病（CML）较为合适。
Aims To assess the dose selection using population pharmacokinetics of Pegylated Intron-alpha 2b (PEG-Intron) in patients with chronic myelogenous leukaemia (CML).Methods PEG-Intron 3-6 mu g kg(-1) was administered subcutaneously once a week and blood samples were collected up to 48 weeks of treatment. A total of 624 samples collected from 137 patients were included in the analysis. Nonlinear mixed-effects modelling was used to analyse the sparsely sampled concentration data from a clinical efficacy trial. Covariates in the analysis included weight, sex, age, race, serum creatinine and estimated creatinine clearance (CLcr).Results The apparent clearance of PEG-Intron decreased after repeated dosing. The clearance at treatment week 4 was 42.3 l day(-1) (patients with CLcr 120 ml min(-1)) with interpatient variability 30%. At treatment week 48, the clearance value was reduced to 69% of its week 4 value. CLcr, a composite variable calculated from body weight, sex, age and serum creatinine, had a small but statistically significant influence on the clearance of PEG-Intron. The clearance of PEG-Intron in patients with CML was 40% higher than that of hepatitis C virus-infected patients.Conclusion The dose of PEG-Intron 6.0 mu g kg(-1) week(-1) appeared appropriate in the treatment of patients with CML.