PHARMACOKINETICS OF MITOXANTRONE IN HUMANS FOLLOWING SINGLE-AGENT INFUSION OR INTRAARTERIAL INJECTION THERAPY OR COMBINED-AGENT INFUSION THERAPY
PHARMACOKINETICS OF MITOXANTRONE IN HUMANS FOLLOWING SINGLE-AGENT INFUSION OR INTRAARTERIAL INJECTION THERAPY OR COMBINED-AGENT INFUSION THERAPY
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DOI：
10.1007/bf00253059
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发表时间：
1986-01-01
影响因子：
3
通讯作者：
MCVIE, JG
中科院分区：
文献类型：
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作者：
VANBELLE, SJP;DEPLANQUE, MM;MCVIE, JG
本研究描述了米托蒽醌的药代动力学测定的一个敏感和具体的高效液相色谱法。接受治疗的患者（15 mg/m2，持续30 min）符合三室模型，T1/2α为1/2 min，T1/2β为93 min，缓慢消除相为36 h。中央室容积为26.22，分布容积为1381.9。测定了5例接受米托蒽醌12 mg/m2、氨甲喋呤30 mg/m2和长春新碱2 mg联合化疗的患者的药代动力学参数。这些结果与单药治疗的结果没有差异，除了中央室的体积显著减少。肝动脉输注米托蒽醌后的峰值水平比同一患者静脉注射相同剂量的米托蒽醌后的峰值水平低3倍。胸水采样显示与血浆水平相比增加了6倍（12 ng/ml vs. 2 ng/ml）。数据的多元线性回归分析显示药代动力学结果与一些基线参数之间存在相关性。根据这些关系，可以预测米托蒽醌动力学行为的变化，但另一方面，从基线参数或药代动力学结果中，毒性的预测性较低。
This study describes the pharmacokinetics of mitoxantrone determined by a sensitive and specific HPLC-method.The time-concentration curves of i.v.-treated patients (15 mg/m2over 30 min) correspond to a three-compartment model with a T1/2α of 12 min, a T1/2β of 93 min, and a slow elimination phase of 36 h.The central compartment volume was 26.22 and the distribution volume, 1381.9. The mean urinary excretion was 4.9% of the total dose.The pharmacokinetic parameters were also defined in five patients who were treated with combination chemotherapy (mitoxantrone 12 mg/m2, methotrexate 30 mg/m2and vincristine 2 mg). These results were not different from those with the single-drug treatment, except for the volume of the central compartment, which was significantly decreased. The peak levels after hepatic arterial infusion of mitoxantrone were three times lower than those after the identical dose given i.v. to the same patient. Pleural fluid sampling showed a six-fold increase compared with the plasma level (12 ng/ml versus 2 ng/ml).A multiple linear regression analysis of the data revealed correlations between the pharmacokinetic results and some of the baseline parameters. It is possible to predict changes in the kinetic behaviour of mitoxantrone on the basis of these relations but on the other hand toxicity is less predictable from the baseline parameters or from the pharmacokinetic results.