Cisplatin pharmacokinetics in children with cancer
Cisplatin pharmacokinetics in children with cancer
复制标题
DOI：
10.1016/s0959-8049(97)00341-9
复制
发表时间：
1997-10-01
影响因子：
8.4
通讯作者：
Newell, DR
中科院分区：
文献类型：
--
作者：
Peng, B;English, MW;Newell, DR
顺铂是一种治疗许多儿科癌症的重要药物，尽管广泛使用，但关于该药物在儿童中的药代动力学数据非常有限。21例患者静脉滴注50-120 mg/m2顺铂24 h后，研究了顺铂的药代动力学。采用原子吸收分光光度法测定血浆中总铂和游离铂（Pt）水平以及尿中Pt水平。通过非房室和房室分析确定药代动力学参数。对于给定的基于表面积的顺铂剂量，游离药物暴露量（血浆浓度-时间曲线下面积- AUC）存在3倍的患者间变异性。游离铂的平均（+/- SD）药代动力学参数为：AUC 0.47 +/- 0.13 mg/ml.min/100 mg/m（2），V-dss 12.5 +/- 2.7 l/m（2），t（1/2）39 +/- 9 min，Ke 0.019 +/- 0.006 min（-1），Cl-肾62 ml/min/m（2），Cl-总量233 +/- 455 ml/min/m（2），Cp-ss 0.31 +/- 0.09 μ g/ml。总游离铂清除率比肾小球滤过率（GFR）高1.5-5.8倍（3.4 +/- 1.0）。顺铂的肾脏清除率与GFR无关，顺铂仅通过有限的尿液排泄（0-48 h给药剂量的27%），表明除肾脏清除外，还有其他重要的清除途径。患者和治疗异质性预先回避了药代动力学-药效学关系的研究;然而，观察到的患者间药代动力学变异程度表明，儿童中基于体表面积的顺铂给药并不令人满意。(C)1997 Elsevier Science Ltd.
Cisplatin is an important drug in the treatment of a number of paediatric cancers yet, despite widespread use, there are only very limited data on the pharmacokinetics of the drug in children. Cisplatin pharmacokinetics were studied in 21 patients following a 24 h infusion of 50-120 mg/m(2) cisplatin. Total and free platinum (Pt) levels in plasma and Pt in urine, were measured by atomic absorption spectrophotometry. Pharmacokinetic parameters were determined by non-compartmental and compartmental analyses. There was 3-fold interpatient variability in free drug exposure (area under the plasma concentration versus time curve - AUC) for a given surface area-based dose of cisplatin. The mean (+/- SD) pharmacokinetic parameters for free Pt were: AUC 0.47 +/- 0.13 mg/ml.min/100 mg/m(2), V-dss 12.5 +/- 2.7 l/m(2), t(1/2) 39 +/- 9 min, Ke 0.019 +/- 0.006 min(-1), Cl-renal 62 ml/min/m(2), Cl-total 233 +/- 455 ml/min/m(2), Cp-ss 0.31 +/- 0.09 mu g/ml. The total free Pt clearance was 1.5-5.8-fold higher (3.4 +/- 1.0) than the glomerular filtration rate (GFR). The renal clearance of cisplatin was not related to GFR and cisplatin was subject to only limited urinary excretion (27% administered dose 0-48 h), indicating that there are other important pathways of clearance beside renal elimination. Patient and treatment heterogeneity pre eluded the investigation of pharmacokinetic-pharmacodynamic relationships; however, the degree of interpatient pharmacokinetic variability observed suggests that body surface area-based dosing of cisplatin in children is not satisfactory. (C) 1997 Elsevier Science Ltd.