紫杉醇的抗肿瘤作用、药理及药代动力学研究  

STUDIES ON THE PHARMACODYNAMICS AND PHARMACOKINETICS OF PACLITAXEL

作　　者：韩锐[1] 何小庆[1] 刘红岩[1] 雷小虹[1] 程青[1] 

机构地区：[1]中国医学科学院,中国协和医科大学药物研究所

出　　处：《中国新药杂志》1996年第4期248-251,共4页Chinese Journal of New Drugs

摘　　要：药理试验证明紫杉醇能有效抑制多种人癌细胞，包括ＫＢ细胞、ＨＣＴ－８、Ａ２７８０及ＭＣＦ－７细胞的生长，ＩＣ５０分别为０．００１９，０．００３６及０．０１μｇ／ｍｌ。实验治疗指出，紫杉醇对黑色素瘤Ｂ－１６，Ｗａｌｋｅｒ癌肉瘤及对裸鼠的人卵巢癌异种移植瘤的生长有明显抑制作用。药理研究显示紫杉醇可促进微管蛋白聚合并抑制其解聚；明显影响Ｌ－１２１０细胞的周期移行，使细胞阻断在Ｇ２＋Ｍ期。此外，还出现多倍体细胞群体。药代动力学参数：ｔ１／２α为０．１２ｈ，ｔ１／２β为５．０２ｈ，ＡＵＣ为１１．８２（μｇ·ｈ）／ｍｌ，Ｖｃ为０．５０Ｌ／ｋｇ，ＣＬｓ为０．４２Ｌ／（ｈ·ｋｇ）Pharmacological studies demonstrated that paclitaxel is very active in the inhibition of the growth of human cancer cell panel including KB cells.HCT 8,A2780,and MCF 7 cells.The IC 50 is as low as 0.0019,0.0036,and 0.01 μg/ml respectively.Experimental therapeutic studies indicated that paclitaxel significantly inhibited the growth of melanoma B 16,Walker carcinosarcoma and heterotransplanted human ovarian cancer in nude mice.Biochemical pharmacological studies showed that paclitaxel can accelerate microtubule assembly and inhibit its deassembly;population in GI was decreased while the cell population in G 2+M phase was increased significantly.In addition, a polyploid cell population appeared.Pharmacokinetic studies demonstrated that the t 1/2 alpha was 0.12 h and t 1/2 beta was 5.02 h when it was injected intravenously at a dose of 5 mg/kg in rats.The AUC,Vc and CLs were 11.82(μg·h)/ml,0.50 L/kg and 0.42 L/(h·kg) respectively.

关 键 词：紫杉醇 药效学 药代动力学 药理 

分 类 号：R979.1[医药卫生—药品]