IN-VIVO MICRODIALYSIS STUDY OF THE DISTRIBUTION OF CISPLATIN INTO BRAIN-TUMOR TISSUE AFTER INTRACAROTID INFUSION IN RATS WITH 9L MALIGNANT GLIOMA

Simultaneous brain microdialysis in tumour and non-tumour tissues has been used for kinetic determination of the local distribution of an an ticancer agent, cisplatin, in rats. Rat brain was implanted with 9L ma lignant glioma and cisplatin (3.5 mg kg(-1)) was administered as a sel ective intracarotid infusion for 30 min to rats prepared for brain mic rodialysis. The amount of platinum in the dialysate collected from tum our and non-tumour brain tissues was determined by atomic absorption s pectrophotometry, as representative of cisplatin. Total and free plati num concentrations in plasma were also measured. Free platinum is accu mulated preferentially in the tumour tissue and the brain tumour distr ibution coefficient (the ratio of brain tumour platinum AUC to plasma free platinum AUG, where AUC is the area under the platinum concentrat ion-time curve) was 0.69, although there was little distribution into normal brain tissue. Drug binding to plasma proteins was 65%. It is co ncluded that simultaneous microdialysis is an easy and available metho d for assessing in-vivo local pharmacokinetics and distribution of cis platin in tumour and non-tumour tissues of the brain.