Blöchl-Daum B, Müller M, Meisinger V, Eichler H G, Fassolt A, Pehamberger H
Department of Clincal Pharmacology, Vienna University Hospital, Austria.
Br J Cancer. 1996 Apr;73(7):920-4. doi: 10.1038/bjc.1996.164.
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.) microgram/ml, 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.
抗癌药物的临床抗肿瘤疗效取决于剂量强度，即肿瘤组织中的浓度-时间曲线。因此，关于肿瘤中药物浓度曲线的信息至关重要，但缺乏合适的测量方法。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-时间曲线，从而评估微透析在人体肿瘤药代动力学研究中的应用范围。对6例四肢或躯干皮肤黑色素瘤转移患者进行了研究，这些患者计划接受卡铂（400mg/m²静脉注射）治疗。监测了血清、肿瘤内和皮下组织中的卡铂浓度。使用反向透析法在体外和体内对微透析探针进行了校准。获得了肿瘤和皮下组织中完整的卡铂浓度随时间变化的曲线。计算了主要药代动力学参数（最大浓度、达到最大浓度的时间、曲线下面积、消除半衰期），并得出了卡铂的组织和肿瘤/血清浓度比。皮肤黑色素瘤转移灶中卡铂的平均游离浓度仅达到血清总水平的约50%-60%；肿瘤内最大浓度为7.6（±2.0；标准误）μg/ml，皮下组织中的平均浓度与肿瘤中的相似。本研究表明，微透析是一种在人体体内测量实体瘤中药物浓度的新工具，似乎是肿瘤药代动力学/药效学研究中有价值的补充。
