碳铂颈动脉给药的临床前药理

Preclinical pharmacology of carboplatin by intracarotid infusion in rats

我们用 G422小鼠胶质瘤株作了顺铂和碳铂的药效比较;用大鼠作了不同给药途径脑摄取药物的比较,其结果是:碳铂与顺铂对 G422小鼠胶质瘤的生长抑制率接近;大鼠颈动脉与股静脉灌注碳铂10mg/kg,用无火焰原子吸收光度法检测脑组织与血浆中铂,结果于血脑屏障开放后颈动脉给药,30分钟灌注侧脑半球铂含量为116.46±8.8μg/g,比对侧提高8倍,未经血脑屏障开放颈动脉给药鼠,30分钟灌注侧半球铂量为75.45±1.65μg/g,比对侧提高3倍,同时间的血浆铂均低于脑组织铂含量10倍,股静脉给药后4小时,脑组织铂已检测不到,而颈动脉给药鼠的灌注侧半球铂含量仍可达5.26±0.48μg/g。大鼠颈动脉与股静脉给药的药代动力学均呈二室开放模型,参数分别为:分布相半衰期T_(1/2)α;动脉:2.86分钟;静脉:3.32分钟;消除相半衰期 T_(1/1)β;动脉:80.10分钟;静脉:136.00分钟。

The anti-neoplasm efficiency of cisplatinand carboplatin was compared in chemicallyinduced mouse glioblastoma (G422).The plat-inum content in brain tissues and blood plasmahas been determined following 10mg/kg ofcarboplatin infused by intracarotid artery orfemoral vein.All results were obtained:thetumor growth inhibiting rate was 61% for car-boplatin 36.4mg/kg (about 1/3LD_(50),and70.2% for cisplatin 4mg/kg (about 1/2 LD_(50)After carboplatin infused by intracarotid thir-ty minutes,the platinum in the ipsilateralcerebral hemisphere was 116.46±8.8μg/gand 14.07±2.08μg/g on the contralateral sidethat the rats were treated with (30% mannitolfor osmotic opening) the blood brain barrier(BBB).If no treatment with mannital therewere 75.45±1.65μg/g and 25.59±2.54μg/g.Plasma concentration of platinum for bothabove groups was 11.31±0.56μg/ml and8.18±2.02μg/ml respectively at the sametime.Fourth hr.after carboplatin adminis-tered by femoral vein the platinum could notdetected in the brain tissues but 5.56±0.48μg/g and 1.25±0.38μg/g of platinumwere found in the carotid infused animals.