Measurement of extracellular fluid carboplatin kinetics in melanoma metastases with microdialysis
Measurement of extracellular fluid carboplatin kinetics in melanoma metastases with microdialysis
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DOI：
10.1038/bjc.1996.164
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发表时间：
1996-04-01
影响因子：
8.8
通讯作者：
Pehamberger, H
中科院分区：
文献类型：
--
作者：
BlochlDaum, B;Muller, M;Pehamberger, H
抗癌药物的临床抗肿瘤效应是剂量强度的函数，即在肿瘤组织中的浓度-时间分布。因此，关于肿瘤中药物浓度分布的信息至关重要，但缺乏适当的测量方法。本研究的目的是通过微透析采样获得模型抗癌药物卡铂在实体瘤(黑色素瘤)中的浓度-时间分布，从而评估微透析在人体肿瘤药代动力学研究中的范围。6例四肢或躯干转移的皮肤黑色素瘤患者，计划接受卡铂(400 mg m(-2)静脉注射)。，并对其进行了研究。监测卡铂在血清、肿瘤内和皮下组织中的浓度。采用反透析法在体外和体内对微透析探针进行校准。获得了完整的卡铂在肿瘤和皮下组织中的浓度随时间的曲线。计算了组织的主要药动学参数(最大浓度、达到最大浓度的时间、曲线下面积、消除半衰期)，并求出了卡铂的肿瘤/血清浓度比。皮肤黑色素瘤转移瘤中卡铂的平均游离浓度仅为血清总浓度的50-60%；肿瘤内最大浓度为7.6(+/-2.0；S.E.M.)Mgml(-1)，皮下组织中的平均浓度与肿瘤中的浓度相似。本研究表明，微透析是一种测量体内人体实体肿瘤药物浓度的新工具，对肿瘤学中的药代动力学/药效学研究具有重要的补充价值。
Clinical anti-tumour efficacy of anti-cancer drugs is a function of dose intensity, i.e. the concentration-time profile in tumour tissue. Hence, information on drug concentration profiles in tumours is of critical importance but appropriate methods for measurement are lacking. The aim of the present study was to obtain, by microdialysis sampling, concentration-time profiles in a solid tumour (melanoma) of a model anti-cancer drug, carboplatin, and thereby to assess the scope of microdialysis for tumour pharmacokinetic studies in man. Six patients with cutaneous melanoma metastases at the extremities or body trunk, scheduled to receive carboplatin (400 mg m(-2) i.v.) were studied. Carboplatin concentrations were monitored in serum, intratumoral and subcutaneous tissue. Calibration of the microdialysis probes was carried out in vitro and in vivo with use of the retrodialysis method. Complete carboplatin concentration vs time profiles in tumour and subcutaneous tissue were obtained. Major pharmacokinetic parameters (maximum concentration, time to maximum concentration, area under the curve, elimination half-life) were calculated for tissues and tumour/serum concentration ratios for carboplatin were derived. Mean free concentrations of carboplatin in cutaneous melanoma metastases reached only about 50-60% of total serum levels; maximal intratumoral concentrations were 7.6 (+/-2.0; s.e.m.) mu g ml(-1), mean concentrations in subcutaneous tissue were similar to those in tumour. The present study demonstrates that microdialysis is a novel tool for measuring drug concentrations in solid tumours in humans in vivo and appears to be a valuable addition for pharmacokinetic/pharmacodynamic studies in oncology.