复方脑肽节苷脂注射液对大鼠细胞色素P450酶亚型活性的影响  

Effect of compound brain peptide ganglioside injection on the activity of cytochrome P450 isoforms in rats

作　　者：刘凡琪 李自强[1] 黄宇虹[1] 王保和[3] LIU Fan-qi;LI Zi-qiang;HUANG Yu-hong;WANG Bao-he(Clinical Pharmacology Center,Second Affiliated Hospital of Tianjin UniversitYy of Traditional Chinese Medicine,Tianjin 300250,China;Graduate School,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Traditional Chinese Medicine Hall,First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China)

机构地区：[1]天津中医药大学第二附属医院临床药理中心,天津300250 [2]天津中医药大学研究生院,天津301617 [3]天津中医药大学第一附属医院国医堂,天津300193

出　　处：《中国临床药理学杂志》2023年第20期2989-2994,共6页The Chinese Journal of Clinical Pharmacology

基　　金：天津市教委科研计划基金资助项目(2021ZD030)。

摘　　要：目的 考察复方脑肽节苷脂注射液对细胞色素P450(CYP)1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6和CYP3A4活性的影响。方法 将大鼠随机分为对照组和实验组,实验组每日尾静脉注射复方脑肽节苷脂注射液1.8 mL·kg^(-1),对照组给予0.9%NaCl,共10 d。最后一次给药30 min后,2组均灌胃Cocktail探针溶液(茶碱、安非他酮、瑞格列奈、甲苯磺丁脲、奥美拉唑、美托洛尔、咪达唑仑)。在不同时间点采血,用LC-MS检测各探针的血药浓度,计算7个探针药的药代动力学参数,评价相应CYP450酶亚型的体内代谢活性。结果 对照组瑞格列奈的AUC_(0-t)为(942.01±234.99) ng·h·mL^(-1),AUC_(0-∞)为(970.62±232.35) ng·h·mL^(-1),清除率(CL)为(328.28±83.20) L·h·kg^(-1),而实验组瑞格列奈的AUC_(0-t)为(1 740.40±720.71) ng·h·mL^(-1),AUC_(0-∞)为(1 757.03±714.44) ng·h·mL^(-1),CL为(202.53±81.49) L·h·kg^(-1),与对照组相比,瑞格列奈的AUC_(0-t)、AUC_(0-∞)分别显著增加1.85倍、1.81倍,CL显著降低了38.31%,其他探针药物的药代动力学参数差异无统计学意义。结论 复方脑肽节苷脂注射液可抑制CYP2C8的活性,而对CYP1A2、CYP2B6、CYP2C9、CYP2C19、CYP2D6和CYP3A4无显著影响。Objective To investigate the effect of compound brain peptide ganglioside injection on the activities of cytochrome P450 (CYP)1A2,CYP2B6,CYP2C8,CYP2C9,CYP2C19,CYP2D6 and CYP3A4.Methods The rats were randomly divided into the control group and the experimental group.The experimental group was injected with compound brain peptide ganglioside injection 1.8 m L·kg^(-1)through tail vein every day,and the control group was given 0.9%NaCl for 10 days.After the last administration of 30 min,Cocktail probe solutions (theophylline,bupropion,repaglinide,tolbutamide,omeprazole,metoprolol,midazolam) were intragastric administration to both groups.Blood samples were collected at different time points,the plasma concentrations of each probe were detected by LC-MS,the pharmacokinetic parameters of 7 probe drugs were calculated,and the metabolic activity of the corresponding CYP450 enzyme subtypes in vivo was evaluated.ResultsThe AUC_(0-t)of repaglinide in control group was (942.01±234.99)ng·h·m L^(-1),AUC_(0-∞)was (970.62±232.35) ng·h·m L^(-1),and clearance (CL) was (328.28±83.20)L·h·kg^(-1).In the experimental group,the AUC_(0-t)of repaglinide was (1 740.40±720.71) ng·h·m L^(-1),AUC_(0-∞)was (1 757.03±714.44) ng·h·m L^(-1),and CL was (202.53±81.49) L·h·kg^(-1).Compared with the control group,AUC_(0-t)and AUC_(0-∞)of repaglinide significantly increased by 1.85 times and 1.81 times,while CL significantly decreased by 38.31%.The pharmacokinetic parameters of other probe drugs had no significant difference.Conclusion Compound porcine cerebroside and ganglioside injection could inhibit the activity of CYP2C8,but had no significant effect on CYP1A2,CYP2B6,CYP2C9,CYP2C19,CYP2D6 and CYP3A4.

关 键 词：复方脑肽节苷脂注射液 细胞色素P450 药代动力学 COCKTAIL探针药物法 

分 类 号：R28[医药卫生—中药学]