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[持续静脉输注5-氟尿嘧啶期间干扰素α2b与5-氟尿嘧啶之间的药物相互作用]

[Drug interactions between interferon alpha 2b and 5-fluorouracil during continuous intravenous 5FU infusion].

作者信息

Czejka M, Schüller J, Schernhammer E, Bandak S

机构信息

Institut für Pharmazeutische Chemie, Universität Wien, Osterreich.

出版信息

Pharmazie. 1995 Jun;50(6):416-9.

PMID:7651979
Abstract

The concentration-time profile of 5-fluorouracil (5FU) in serum of patients during continuous infusion of 5FU for five days was investigated. The coadministration of each of 5 million units interferon-alpha-2b (IFN) on day 2 and 4 of the infusion causes an accumulation of 5FU in the serum at about 120% on day 3 in compare to the control (day 1 of infusion without IFN). On day 5 of the infusion the mean 5FU serum concentrations are about 170% higher than on day 1 with a level of probability ranging from p < 0.0003 to p < 0.043. Mean AUC-values increase from 5454 ng/ml.h (day 1) to 12069 ng/ml.h (day 3, p < 0.05) and subsequently to 14919 ng/ml.h on day 5 (p < 0.005). IFN causes an decrease of the total body clearance from 2949 ml/h (day 1) to 1959 ml/h on day 3 and to 1258 ml/h on day 5 (p < 0.008), respectively. There might exist a linear correlation between the order of magnitude of the 5FU serum concentrations and its pharmacokinetic parameters on day 1, 3 and 5 and the administration of IFN, because a close correlation ranging from R = 0.972 to R = 0.999 have been found in regression analysis.

摘要

对患者连续五天输注5-氟尿嘧啶(5FU)期间血清中5FU的浓度-时间曲线进行了研究。在输注的第2天和第4天联合给予500万单位的α-2b干扰素(IFN),与对照组(输注第1天未使用IFN)相比,在第3天血清中5FU的蓄积量约为120%。在输注的第5天,5FU血清平均浓度比第1天高约170%,概率水平范围为p < 0.0003至p < 0.043。平均AUC值从5454 ng/ml·h(第1天)增加到12069 ng/ml·h(第3天,p < 0.05),随后在第5天增加到14919 ng/ml·h(p < 0.005)。IFN使总体清除率分别从2949 ml/h(第1天)降至第3天的1959 ml/h和第5天的1258 ml/h(p < 0.008)。在第1天、第3天和第5天,5FU血清浓度的数量级与其药代动力学参数以及IFN的给药之间可能存在线性相关性,因为在回归分析中发现相关系数R从0.972到0.999的密切相关性。

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