多西紫杉醇对SD大鼠CYP3A1代谢酶活性影响的观察  

Effects of docetaxel on activity of CYP3A1 in SD rats

作　　者：黄红兵[1] 邓多[2] 刘韬[1] 周峰[2] 林子超[1] 陈倩超[1] 陈杰[3] 赵立子 毕惠嫦 

机构地区：[1]华南肿瘤学国家重点实验室中山大学附属肿瘤医院药剂科,广东广州510060 [2]中山大学药学院药学院,广东广州510080 [3]中山大学附属第一医院药学部,广东广州510080 [4]药学院临床药理研究所,广东广州510080

出　　处：《中华肿瘤防治杂志》2009年第15期1135-1138,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：广东省医院药学研究基金(2008A007)

摘　　要：目的:研究抗癌药多西紫杉醇(DOC)对SD大鼠肝细胞CYP3A1代谢酶的影响。方法:将20只雄性SD大鼠随机分为空白对照组(尾静脉推注给予生理盐水,1mL/只,1次/d,连续3d)、地塞米松诱导组〔灌胃给予地塞米松,100mg/(kg·d),连续3d〕、DOC高剂量实验组〔尾静脉推注给予DOC,30mg/(kg·d),连续3d〕、DOC低剂量实验组〔尾静脉推注给予DOC,20mg/(kg·d),连续3d〕。采用HPLC法检测以睾酮为探针药物经大鼠肝微粒体温孵后转化的代谢产物6β-羟基睾酮的生成速率,以评价各组间CYP3A1酶的活性。结果:DOC高、低剂量组6β-羟基睾酮的生成速率,分别为(221.1±79.7)和(254.5±189.8)ρmol/mgproteinmin,空白对照组和地塞米松组分别为(249.1±81.4)和(1781.4±507.7)ρmol/mgpro-teinmin;经统计学检验表明,DOC高、低剂量组6β-羟基睾酮的生成速率与地塞米松诱导组的差异有统计学意义,P<0.01,与空白对照组的差异无统计学意义,P>0.05。结论:DOC对大鼠肝细胞CYP3A1酶活性无诱导作用。OBJECTIVE： To investigate the effects of docetaxel on activity of liver rnicrosome cytochrome P450 3A1 in SD rats. METHOD： Twenty male SD rats were randomly grouped and treated with physiological saline （NS, 1 mI. each rat, iv, 3 d ）, dexamethasone [ DEX, 100 mg/（kg·d）, po, 3 d], high dose of docetaxel （HD, 30 mg/（kg·d）, iv, 3 d] and low dose of docetaxel [LD, 20 mg/（kg, d）, iv, 3 d], respectively. The HPLC-UV method was established and validated to determine the productive velocity of metabolite （6β hydroxyl testosterone, 6β-OHT） of testosterone （as substrate of CYP3A1） and to measure the activity of CYP3A1. RESULT： The productive velocities of 6i3 OHT of the HD, LD, NS and DEX groups were （221.1±79.7）, （254.5±189.8）, （249.1±81.4） and （1 781±507.7） pmol/mg proteinomin, respectively. The HD and LD groups had significant differences compared with the dexamethasone group（P〈0.01）, but there was no significant difference between the docetaxel groups and the control group （P〉 0.05 ）. CONCLUSION： Docetaxel has no inducible effect on the enzymic activity of CYP3A1 in rats.

关 键 词：紫杉 /药理学 细胞色素P450酶系统 色谱法 高效液相 

分 类 号：R96[医药卫生—药理学]