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阿霉素、阿霉素醇及安替比林在肝脏中度肿瘤受累患者中的药代动力学

Pharmacokinetics of adriamycin, adriamycinol, and antipyrine in patients with moderate tumor involvement of the liver.

作者信息

Preiss R, Matthias M, Sohr R, Brockmann B, Hüller H

机构信息

Department of Clinical Pharmacology, Charité Humboldt University, Berlin, German Democratic Republic.

出版信息

J Cancer Res Clin Oncol. 1987;113(6):593-8. doi: 10.1007/BF00390872.

Abstract

The pharmacokinetics of adriamycin, its metabolite adriamycinol, and antipyrine were studied in 17 patients with moderate tumor involvement of the liver and compared to that of 19 tumor patients with normal liver function (Preiss et al. 1985). The individual liver function parameters deviated from normal by a factor ranging from 2.5 to 12.2. The t1/2 alpha and t1/2 beta, the AUC (corrected for body weight and dose) and the total body clearance (CL, corrected for body weight) of adriamycin did not differ significantly between the two groups of patients. Likewise, there was no difference in the kinetic parameters of antipyrine between the two groups. Unlike adriamycin and antipyrine, adriamycinol was found to have a significantly longer t1/2term (60.5 vs 28.3 h, P less than 0.001), an increased AUC (3.00 vs 1.43 h/ug per ml, P less than 0.02), and a higher AUCadriamycinol/AUCadriamycin ratio (0.94 vs 0.52, P less than 0.02) in patients with moderate tumor involvement of the liver. The CL, the AUC, and t1/2 beta of adriamycin correlated significantly (P less than 0.001 and P less than 0.01) with the corresponding kinetic parameters of antipyrine, but not with the usual liver function parameters. No correlation could be found between the kinetic parameters of adriamycinol and those of antipyrine.

摘要

对17例肝脏有中度肿瘤累及的患者进行了阿霉素、其代谢产物阿霉素醇和安替比林的药代动力学研究,并与19例肝功能正常的肿瘤患者进行了比较(Preiss等人,1985年)。个体肝功能参数偏离正常范围的倍数在2.5至12.2之间。两组患者阿霉素的t1/2α和t1/2β、AUC(根据体重和剂量校正)以及全身清除率(CL,根据体重校正)没有显著差异。同样,两组之间安替比林的动力学参数也没有差异。与阿霉素和安替比林不同,在肝脏有中度肿瘤累及的患者中,发现阿霉素醇的t1/2期明显更长(60.5对28.3小时,P小于0.001),AUC增加(3.00对1.43小时/微克每毫升,P小于0.02),且阿霉素醇/AUC阿霉素比值更高(0.94对0.52,P小于0.02)。阿霉素的CL、AUC和t1/2β与安替比林的相应动力学参数显著相关(P小于0.001和P小于0.01),但与常规肝功能参数无关。在阿霉素醇和安替比林的动力学参数之间未发现相关性。

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