奥拉西坦对肝微粒体酶CYP2C9活性的影响研究

Effects of Oxiracetam on the Activity of Hepatomicrosome Enzyme CYP2C9

目的:考察奥拉西坦对肝微粒体酶CYP2C9活性的影响。方法:将大鼠随机分为对照组和实验组,每组18只,对照组每天灌胃蒸馏水,实验组每天灌胃奥拉西坦80 mg/kg,每日2次,连续8 d。第8天灌胃后两组大鼠均立即灌胃给予CYP2C9的探针药物甲苯磺丁脲50 mg/kg,并于给予甲苯磺丁脲后0.25、0.5、0.75、1、1.5、2、3、4、6、10、12、24 h内眼内眦取血。采用高效液相色谱法测定血药浓度,拟合药动学参数,并对两组药动学参数进行比较。结果:对照组与实验组主要药动学参数t1/2分别为(5.45±1.98)、(6.54±1.45)h,cmax分别为(169.12±58.14)、(146.19±49.44)mg/L,AUC0-24 h分别为(1 113.01±264.32)、(1 120.14±208.91)mg·h/L,Vd分别为(0.77±0.32)、(0.91±0.40)L/kg,CL分别为(0.08±0.03)、(0.08±0.02)L/(h·kg),两组间比较差异无统计学意义(P>0.05)。结论:奥拉西坦对甲苯磺丁脲在大鼠体内的药动学未见明显影响,初步认为奥拉西坦对经CYP2C9代谢的药物的药动学无明显影响。

OBJECTIVE：To investigate the effects of oxiracetam on the activity of hepatomicrosome enzyme CYP2C9.METHORDS：Rats were randomly divided into control group and test group with 18 rats in each group.Control group was given distilled water intragastrically,while test group was given oxiracetam（80 mg/kg）intragastrically,twice a day,for consecutive 8 d.Both groups were given hepatomicrosome enzyme CYP2C9 probe tolbutamide（50 mg/kg）intragastrically on the eighth day immediately after gavage;the blood samples were collected from epicanthal folds within 0.25,0.5,0.75,1,1.5,2,3,4,6,10,12,24 h after tolbutamide.The blood concentrations of tolbutamide were determined by HPLC.The pharmacokinetic parameters of the two groups were calculated and compared.RESULTS：The main pharmacokinetic parameters of control group and test group were as follows：t1/2were（5.45±1.98）h vs.（6.54±1.45）h;cmax：（169.12±58.14）mg/L vs.（146.19±49.44）mg/L;AUC0-24 h：（1 113.01±264.32）mg·h/L vs.（1 120.14±208.91）mg·h/L;Vd：（0.77±0.32）L/kg vs.（0.91±0.40）L/kg;CL：（0.08±0.03） L/（h·kg）vs.（0.08±0.02）L/（h·kg）.There was no significant difference between 2 groups（P〉0.05）.CONCLUSIONS：The pharmacokinetics of tolbutamide in rats has no significant change after treated with oxiracetam;it is preliminary considered that oxiracetam has no obvions effect on the products metabolized by CYP2C9.