An attempt to analyze the concentration of the chemotherapeutic agents in the extracellular fluid of the experimental brain tumor tissue using microdialysis technique

化疗药物在体外和体内的疗效有时会有所不同。导致这一现象的一个重要因素可能是肿瘤组织中化疗药物的实际浓度。然而，化疗药物浓度的评估在技术上是困难的，方法也没有建立。我们成功地利用微透析法分析了脑肿瘤组织细胞外液中的药物浓度。本研究使用的化疗药物为ACNU和顺铂。药物在细胞外液中的实际浓度(指y)可根据通过以下演算通过体外微透析获得的样品的药物浓度(指x)来计算。ACNU：Y=8.36X-0.065，顺铂：Y=8.43X+0.086。在9L大鼠脑胶质瘤中，药物浓度在20min时最高(5.41μg/ml)，然后在静脉注射ACNU 10 mg时逐渐下降。静脉注射顺铂2 mg，10min时血药浓度最高，为12.3μg/ml。在脑转移瘤(ACL15)中，阿昔洛韦10 mg给药20min时血药浓度最高，为2.77μg/ml。而顺铂2 mg给药10min时药物浓度最高(13.3μg/ml)。在两种肿瘤模型中，当给予ACNU 1 mg和顺铂0.2 mg时，药物浓度均低于可检测的水平。这些结果表明，当临床用药时，脑肿瘤组织细胞外液中的药物浓度出人意料地低。提高局部用药水平的尝试是合理的。

The efficacy of chemotherapeutic agents in vitro and in vivo sometimes divergent. One important factor responsible for this phenomenon is likely to be the actual concentration of the chemotherapeutic agent in the tumor tissue. However, the assessment of the concentration of the chemotherapeutic agents is technically difficult, and the methods are not established. We successfully analyzed the drug concentration in the extracellular fluid of the brain tumor tissue by use of microdialysis. The chemotherapeutic agents employed in this study were ACNU and cisplatinum. The actual concentration of the drug in the extracellular fluid (referred to y) is calculable from the drug concentration of the samples (referred to x) obtained by in vitro microdialysis via following calculus. For ACNU : y=8.36x-0.065, for cisplatinum : y=8.43x+0.086In the 9L rat glioma, the drug concentration showed highest value at 20min (5.41μg/ml) followed by a grudual decrease when 10mg of ACNU was administered intravenously. Whereas the drug concentration was highest at 10min (12.3μg/ml) when 2mg of cisplatinum was administered intravenously. In the metastatic brain tumor (ACL15), the drug concentration revealed highest value at 20min (2.77μg/ml) when 10mg of ACNU was administered. In contrast, the drug concentration was highest at 10min (13.3μg/ml) when 2mg of cisplatinum was administered. In the both tumor models, the drug concentration was below the detectable level when 1mg of ACNU and 0.2mg of cisplatinum were administered. These results suggest that the drug concentration in the extracellular fluid of the brain tumor tissue is unexpectedly low when a clinical dosis of the drug is used systemically. An attempt to raise the topical drug level is warranted.