“鸡尾酒法”检测异甘草酸镁对大鼠P450酶影响

发布时间：2018-03-29 01:28

本文选题：细胞色素肝药酶　切入点：鸡尾酒法　出处：《蚌埠医学院》2014年硕士论文

【摘要】：目的：通过“鸡尾酒探针药物法”建立一种快速、简便、灵敏的HPLC方法评价异甘草酸镁对大鼠细胞色素P450代谢酶活动的影响。方法：选取SPF级SD大鼠随机分为单剂量组、多剂量组及实验对照组。探针药物及给药剂量分别为咪达唑仑10mg/kg、右美沙芬5mg/kg、奥美拉唑10mg/kg、茶碱25mg/kg、氯唑沙宗50mg/kg、双氯芬酸5mg/kg。异甘草酸镁注射液的给药剂量为20mg/kg。通过腹腔注射给予探针药物，尾静脉注射给予异甘草酸镁注射液。给药后于一定的时间段从大鼠眼底静脉丛取血0.5ml置于肝素化的离心管中，通过高效液相色谱法检测血浆中探针药物的血药浓度，测得的数据经DAS2.0软件处理得出相关药动学参数。然后通过t检验分析各组之间差异。结果：大鼠体内异甘草酸镁联合用探针药物给药后，右美沙芬、茶碱、双氯芬酸及奥美拉唑药动学参数无显著性变化。单剂量组的探针药物咪达唑仑及多剂量组的探针药物奥美拉唑在大鼠体内某些药动学参数发生显著性变化。结论：异甘草酸镁注射液能够诱导大鼠体内肝药酶CYP2E1的活性及抑制大鼠肝药酶CYP3A4的活性。对大鼠体内细胞色素肝药酶CYP2D6、CYP1A2、CYP2C19及CYP2C9无显著性影响，，提示我们在临床合用异甘草酸镁与CYP2E1及CYP3A4代谢的底物药物时应注意药物的代谢性相互作用。
[Abstract]:Objective: to establish a rapid, simple and sensitive HPLC method to evaluate the effect of magnesium isoliganate on the activity of cytochrome P450 metabolic enzyme in rats. Methods: SPF SD rats were randomly divided into single dose group. The dosage of the probe was 10 mg / kg of midazolam, 5 mg / kg of dextromethorphan, 10 mg / kg of omeprazole, 25 mg / kg of theophylline, 50 mg / kg of clozoxazone, 5 mg / kg of diclofenac and 20 mg / kg of magnesium isoglycyrrhizate. Injected with probe drugs, Magnesium isoglycyrrhizinate was injected into the tail vein. 0.5ml was taken from the fundus venous plexus of rats at a certain time and placed in heparinized centrifuge tube. The blood concentration of the probe drug in plasma was detected by high performance liquid chromatography (HPLC). The relevant pharmacokinetic parameters were obtained by DAS2.0 software, and then the differences among the groups were analyzed by t-test. Results: dextromethorphan, theophylline, dextromethorphan and theophylline were treated with magnesium isoglycyrrhizinate in rats. The pharmacokinetic parameters of diclofenac and omeprazole were not significantly changed. Conclusion: magnesium isoglycyrrhizinate injection can induce the activity of hepatic drug enzyme CYP2E1 and inhibit the activity of rat liver drug enzyme CYP3A4 in vivo, but has no significant effect on cytochrome hepatic enzyme CYP2D6, CYP1A2, CYP2C19 and CYP2C9 in rats. It is suggested that we should pay attention to the metabolic interaction of magnesium isoglycyrrhizinate with substrates of CYP2E1 and CYP3A4.
【学位授予单位】：蚌埠医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965

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