紫杉醇对大鼠肝微粒体CYP3A1的作用  

Effect of paclitaxel on activity of CYP3A1 in rats

作　　者：黄红兵[1] 刘韬[1] 邓多[2] 周峰[2] 林子超[1] 陈倩超[1] 陈杰[3] 赵立子[4] 毕惠嫦[4] 

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,广东广州510060 [2]中山大学药学院,广东广州510080 [3]中山大学附属第一医院,广东广州510080 [4]中山大学药学院临床药理研究所,广东广州510080

出　　处：《中国医院药学杂志》2008年第24期2078-2081,共4页Chinese Journal of Hospital Pharmacy

基　　金：广东省医院药学研究基金资助项目(编号2008A007)

摘　　要：目的:考察紫杉醇对Sprague-Dawley(SD)大鼠肝微粒体细胞色素P4503A1(CYP3A1)酶活性的影响效应。为该药临床应用中可能与其他药物产生的相互作用提供依据。方法:将9只雄性SD大鼠随机分为空白对照组(尾静脉注射给予生理盐水,每只1mL,qd,连续3d)、地塞米松诱导组(灌胃给予地塞米松,100mg·kg-1.d-1,连续3d)、紫杉醇实验组(尾静脉注射给予紫杉醇,6.7mg·kg-1.d-1,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来反映大鼠CYP3A1酶的活性。结果:空白对照组、地塞米松诱导组和紫杉醇组6β-羟基睾酮的生成速率分别为(643.1±6.0),(2671.1±225.7),(724.8±36.6)pmol·(mgprotein)-1·min-1。紫杉醇组6β-羟基睾酮的生成速率与地塞米松诱导组相比差异有极显著性(P<0.01),与空白对照组相比差异无显著性(P>0.05)。结论:紫杉醇对大鼠CYP3A1酶的活性无诱导作用。OBJECTIVE To investigate the effect of paclitaxel on activity of liver microsome cytochrome P450 3A1 in SD rats. METHODS The 9 male SD rats were randomly grouped and treated with control physiological saline （ NS, I mL/each rat, iv, 3 d ）, dexamethasone （DEX, 100 mg·kg^-1 ·d ^-1 , po, 3 d ）, paclitaxel （ PAC, 6. 7 mg·kg^-1 ·d ^-1, iv, 3 d ） , respec tively. 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. RESULTS The produclive velocities of 6β- OHT of control group, DEX and PAC groups were （643.1 ± 6.0）, （2671.1 ± 225.7） and （724. 8 ± 36.6） pmol·（mg protein） ^-1 ·min^-1. The productive velocity of 6β-OHT of paclitaxel group had significant difference compared with dexamethasone group, but there was no significant difference between paclitaxel group and the control group, CONCLUSION Paclitaxel had no inducible effect on the enzymic activity of CYP3A1 in rats.

关 键 词：紫杉醇 睾酮 6β-羟基睾酮 细胞色素3A1 高效液相色谱法 

分 类 号：R969[医药卫生—药理学]