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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 of 2-methyl-1 (4-chlorobenzoyl) -5-benzyloxy-1H-indole-3-acetic acid (GY3) . Methods: By RP-HPLC, 8 rats were given intragastric administration of GY3 solution 45mg / kg 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 plasma concentration, using the DAS2.0 pharmacokinetic software to calculate the pharmacokinetic parameters. Chromatographic conditions: The column was Shimadzu C18, the mobile phase was methanol-0.1% phosphoric acid (76:24), the flow rate was 1 ml / min, the detection wavelength was 253 nm, the column temperature was 25 ℃ and the injection volume was 20 μl. Results: The linear range of the concentration of GY3 was 5.0 ~ 160.0μg / m (lr = 0.9996), the absolute recovery was 96.96% ~ 100.22%. The pharmacokinetic parameters tmax was (2.75 ± 2.32) h, cmax was (22.34 ± 9.61) μg / ml, AUC0-∞ was (187.85 ± 115.08) μg · h / ml and t1 / 2β was (6.99 ± 0.99) h. CONCLUSION: The drug-time curve of GY3 in rats is in accordance with the first-order absorption two-compartment model of extravascular administration.