THE PHARMACOKINETICS OF HIGH-DOSE CARBOPLATIN IN PEDIATRIC-PATIENTS WITH CANCER
THE PHARMACOKINETICS OF HIGH-DOSE CARBOPLATIN IN PEDIATRIC-PATIENTS WITH CANCER
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DOI：
10.1038/clpt.1992.82
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发表时间：
1992-06-01
影响因子：
6.7
通讯作者：
RODMAN, JH
中科院分区：
文献类型：
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作者：
MADDEN, T;SUNDERLAND, M;RODMAN, JH
在18例儿科癌症患者中研究了卡铂的配置，剂量范围为400至700 mg/m2，隔天给药（总剂量为1200至2100 mg/m2）与高剂量依托泊苷。中位年龄为7.7岁，肝功能正常，血清肌酐水平小于或等于1.0 mg/dl。采用原子吸收光谱法测定卡铂的药动学。超滤铂的中位药代动力学参数如下：清除率为45.8 mt/min/m2（范围25.5 ~ 65.3 ml/min/m2），终末半衰期为3.6小时（范围2.1 ~ 14.2小时）。卡铂清除率（CL）值和分布体积（V(C)）与体型高度相关（CL = 55 ×体表面积[BSA，单位平方米]- 6.7,r2 = 0.73， V(C) = 5 × BSA[单位平方米]+ 0.26,r2 = 0.69）。然而，按BSA归一化的卡铂剂量仍导致浓度-时间曲线下面积的2 - 3倍变化。先前接受累积顺铂剂量大于或等于960 mg/m2的受试者（n = 9）卡铂CL显著降低（p < 0.05），但不受年龄、性别或诊断的影响。
Carboplatin disposition was studied in 18 pediatric patients with cancer over a dosage range of 400 to 700 mg/m2 given on an alternate-day schedule (total doses of 1200 to 2100 mg/m2) with high-dose etoposide. Median age was 7.7 years, hepatic functions were normal, and serum creatinine levels were less-than-or-equal-to 1.0 mg/dl. Carboplatin pharmacokinetics were determined by atomic absorption spectroscopy. Median pharmacokinetic parameters for ultrafilterable platinum were as follows: clearance 45.8 mt/min/m2 (range, 25.5 to 65.3 ml/min/m2) and a terminal half-life of 3.6 hours (range, 2.1 to 14.2 hours). Carboplatin clearance (CL) values and volume of distribution (V(C) were highly correlated to body size (CL = 55 x Body surface area in [BSA, in square meters] - 6.7, r2 = 0.73, V(C) = 5 x BSA [in square meters] + 0.26, r2 = 0.69). However, carboplatin doses normalized to BSA still resulted in twofold to threefold variability in area under the concentration - time curve. Carboplatin CL was significantly lower in those subjects (n = 9) who had previously received cumulative cisplatin doses of greater-than-or-equal-to 960 mg/m2 (p < 0.05) but was not influenced by age, gender, or diagnosis.