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阿霉素肝内与静脉内给药——恶性肝肿瘤患者的比较药代动力学研究

Intrahepatic and intravenous administration of adriamycin--a comparative pharmacokinetic study in patients with malignant liver tumours.

作者信息

Eksborg S, Cedermark B J, Strandler H S

出版信息

Med Oncol Tumor Pharmacother. 1985;2(1):47-54. doi: 10.1007/BF02934780.

Abstract

The pharmacokinetics of adriamycin in patients with malignant tumours of the liver were studied after peripheral intravenous treatment and after regional administration of the drug either by the arterial route or by the portal vein, with or without hepatic artery ligation. The plasma concentration of adriamycin after intravenous as well as after intrahepatic administration followed a three-compartment open model. The results in the present study confirm previous reports of a large inter-individual variation of the pharmacokinetics of adriamycin. After intravenous administration the individual variations in AUC/mg/m2 and Cp,max/mg/m2 (dose normalized area under plasma concentration time curve and dose normalized maximum plasma concentration, respectively) were more than 5-fold. The area under the plasma concentration time curve (AUC) was on the average 1.5 times higher after the peripheral intravenous administration than after intrahepatic administration. The reduction of maximum plasma concentration (Cp,max) of adriamycin after intrahepatic administration was even more pronounced than the reduction in AUC (mean value Cp,max iv/Cp,max ihep = 1.7). The plasma concentration of adriamycinol did not exceed 20 ng/ml. The AUC values of adriamycinol were 20% (median value) of the AUC values of adriamycin, indicating the importance of adriamycinol in the adriamycin therapy.

摘要

研究了阿霉素在肝恶性肿瘤患者外周静脉给药以及经动脉或门静脉区域给药(伴或不伴肝动脉结扎)后的药代动力学。静脉给药以及肝内给药后阿霉素的血浆浓度均遵循三室开放模型。本研究结果证实了先前有关阿霉素药代动力学个体间差异很大的报道。静脉给药后,AUC/mg/m²和Cp,max/mg/m²(分别为血浆浓度-时间曲线下剂量标准化面积和剂量标准化最大血浆浓度)的个体差异超过5倍。外周静脉给药后的血浆浓度-时间曲线下面积(AUC)平均比肝内给药后高1.5倍。肝内给药后阿霉素最大血浆浓度(Cp,max)的降低甚至比AUC的降低更明显(平均值Cp,max iv/Cp,max ihep = 1.7)。阿霉素醇的血浆浓度未超过20 ng/ml。阿霉素醇的AUC值为阿霉素AUC值的20%(中位数),表明阿霉素醇在阿霉素治疗中的重要性。

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