新型胰岛素增敏剂2-甲基-1(-4-氯苯甲酰基)-5-苄氧基-1H-吲哚-3-乙酸在大鼠体内的药动学研究  

Pharmacokinetics Study of New Insulin Sensitizer 2-methyl-1-(4-chlorobenzoyl)-5-benzyloxy-1H-indole-3-Acetic Acid in Rats

作　　者：黄静[1] 陆苑[1] 饶光玲[1] 李桂兰[1] 汤磊[1] 

机构地区：[1]贵阳医学院药学院,贵阳550004

出　　处：《中国药房》2013年第25期2314-2316,共3页China Pharmacy

基　　金：国家自然科学基金(No.30960462);贵州省优秀科技教育人才省长专项基金(No.黔科合人字[2009]81号);贵州省优秀青年科技人才培养对象专项资金项目(No.黔科合人字[2009]24);贵州省科学技术基金(No.黔科合J字[2012]2031号)

摘　　要：目的:研究新型胰岛素增敏剂2-甲基-1(-4-氯苯甲酰基)-5-苄氧基-1H-吲哚-3-乙酸(GY3)在大鼠体内的药动学特征。方法:采用反相高效液相色谱法,检测8只大鼠灌胃给予GY3溶液45mg/kg后0.25、0.5、1.5、2.5、4.0、5.0、7.0、9.0、12.0、16.0、20.0、24.0、28.0、36.0h的血药浓度,用DAS2.0药动学软件计算其药动学参数。色谱条件:色谱柱为ShimadzuC18,流动相为甲醇-0.1%磷酸(76∶24),流速为1ml/min,检测波长为253nm,柱温为25℃,进样量为20μl。结果:GY3检测质量浓度的线性范围为5.0～160.0μg/m(lr=0.9996),绝对回收率为96.96%～100.22%。药动学参数tmax为(2.75±2.32)h、cmax为(22.34±9.61)μg/ml、AUC0-∞为(187.85±115.08)μg·h/ml、t1/2β为(6.99±0.99)h。结论:GY3在大鼠体内的药-时曲线特征符合血管外给药一级吸收二室模型。OBJECTIVE：To study the pharmacokinetics characteristics of new insulin sensitizer 2-methyl-1-（4-chlorobenzoyl）-5-benzyloxy-1H-indole-3-acetic acid（GY3）in rats. METHODS：RP-HPLC method was adopted. The blood concentration of GY3 in 8 rats were determined 0.25,0.5,1.5,2.5,4.0,5.0,7.0,9.0,12.0,16.0,20.0,24.0,28.0 and 36.0 h after given 45 mg/ kg. Pharmacokinetic parameters were calculated by the DAS 2.0 software. The determination was performed on Shimadzu C 18 column with mobile phase consisted of methanol-0.1% phosphoric acid（76 ∶ 24）at the flow rate of 1 ml/min. The detection wavelength was set at 253 nm and column temperature was 25 ℃. The sample size was 20 μl. RESULTS：Linear range of GY3 were 5.0-160.0 μg/ml（r=0.999 6）with absolute recovery of 96.96%-100.22%. Pharmacokinetic parameters were as follows：t max was （2.75±2.32）h;c max was（22.34±9.61）μg/ml;AUC 0-∞ was（187.85±115.08）μg· h/ml;t 1/2β was（6.99±0.99）h. CONCLUSIONS： Pharmacokinetic concentration-time curve of GY3 in rats is in line with first-order absorption two-compartment model.

关 键 词：2-甲基-1(-4-氯苯甲酰基)-5-苄氧基-1H-吲哚-3-乙酸 反相高效液相色谱法 大鼠 血药浓度 药动学 

分 类 号：R965[医药卫生—药理学] R587.1[医药卫生—药学]