Boaziz C, Breau J L, Morère J F, Israël L
Service d'Oncologie Médicale, Hôpital Avicenne, Bobigny, France.
Pathol Biol (Paris). 1991 Oct;39(8):789-95.
The blood-brain barrier (BBB) is located between the blood and the extracellular space of the brain. This barrier is formed by the brain capillaries whose endothelial cells have tight intercellular junctions. Transcellular passage of drugs from the bloodstream to the brain occurs selectively, in a manner dependent on the ability of the molecules to penetrale through cell membranes. The blood-brain barrier is one of the main factors of chemotherapy failure in central nervous system tumors. Penetration of a molecule from the bloodstream to the brain is dependent on the compound's liposolubility, expressed by the octanol-water separation coefficient. Following intravenous administration, most drugs fail to achieve adequate levels in the central nervous system for a sufficiently long period of time. A variety of techniques have been used in an attempt to increase CNS penetration of drugs normally shut out by the blood-brain barrier: high-dose chemotherapy, intrathecal injections, intraarterial injections, induction of hyperosmolarity to make the blood-brain barrier permeable. The best results are obtained using liposoluble drugs with optimal octanol-water separation coefficients, such as fotemustine. This compound given as single drug therapy in brain metastases from malignant melanomas has yielded response rates of up to 28.2%.
血脑屏障（BBB）位于血液与脑的细胞外间隙之间。该屏障由脑毛细血管形成，其内皮细胞具有紧密的细胞间连接。药物从血液经细胞转运至脑是选择性发生的，其方式取决于分子穿透细胞膜的能力。血脑屏障是中枢神经系统肿瘤化疗失败的主要因素之一。分子从血液进入脑的穿透取决于化合物的脂溶性，用辛醇 - 水分配系数表示。静脉给药后，大多数药物在足够长的时间内无法在中枢神经系统中达到足够的水平。为了增加通常被血脑屏障阻隔的药物对中枢神经系统的穿透，人们使用了多种技术：大剂量化疗、鞘内注射、动脉内注射、诱导高渗以使血脑屏障通透。使用具有最佳辛醇 - 水分配系数的脂溶性药物可获得最佳效果，如福莫司汀。这种化合物在恶性黑色素瘤脑转移中作为单一药物治疗，有效率高达28.2%。
