陈静雅, 王俊俊, 孟沫然, 陈勇. 冰片对大鼠体内CYP2D诱导作用研究J. 药学学报, 2015,50(4): 459-463.
引用本文: 陈静雅, 王俊俊, 孟沫然, 陈勇. 冰片对大鼠体内CYP2D诱导作用研究J. 药学学报, 2015,50(4): 459-463.
CHEN Jing-ya, WANG Jun-jun, MENG Mo-ran, CHEN Yong. Borneol is an inducer of rat hepatic CYP2D activity in vivoJ. Acta Pharmaceutica Sinica, 2015,50(4): 459-463.
Citation: CHEN Jing-ya, WANG Jun-jun, MENG Mo-ran, CHEN Yong. Borneol is an inducer of rat hepatic CYP2D activity in vivoJ. Acta Pharmaceutica Sinica, 2015,50(4): 459-463.

冰片对大鼠体内CYP2D诱导作用研究

Borneol is an inducer of rat hepatic CYP2D activity in vivo

  • 摘要: 冰片是传统中药,近年来许多文献报道冰片能提高其他药物的生物利用度,促进其他药物进入血脑屏障,因而冰片与其他药物合用可能产生的药物相互作用受到高度重视,但冰片对肝脏细胞色素P450 酶的影响却鲜有报道.本文研究了雄性Wistar 大鼠连续灌胃冰片一周对大鼠肝脏CYP2D 表达与活性以及对CYP2D 探针底物右美沙芬大鼠体内药代动力学的影响.结果表明,冰片(33、100 和300 mg·kg-1·d-1)给药一周对大鼠肝脏CYP2D1 mRNA 和蛋白表达无明显影响,但却显著诱导了CYP2D 活性(P<0.05),分别达到1.71、1.97 和2.89倍.此外,与对照组相比,冰片(300 mg·kg-1·d-1)预给药一周组右美沙芬的达峰浓度Cmax降低了10.6%(P >0.05),曲线下面积AUC0-∞减少了27.5%(P<0.01),清除率CL/F 增大了41.1%(P<0.01),表观分布容积Vz/F 增大了23.1%(P >0.05),表明冰片预给药一周能明显加速CYP2D 探针底物右美沙芬的体内清除.由于冰片对大鼠肝脏CYP2D 活性的诱导作用,提示当冰片与CYP2D 底物药物共用时,可能存在发生代谢性相互作用的风险.

     

    Abstract: Borneol is a traditional Chinese medicine. In the past few years, many studies showed that borneol can improve the bioavailability of other drugs, promoting drugs to cross the blood-brain barrier, so the potential drug interactions between borneol and other medicines have attracted great attention, but the influence of borneol to CYP450 and its isoforms are rarely reported. In this research, male Wistar rats were orally administered by borneol for 7 days, then the mRNA and protein expression and the activities of CYP2D were detected, we also compared the pharmacokinetic parameters of CYP2D's specific substrate between control group and borneol group. The results show that borneol (33, 100 and 300 mg ·kg-1·d-1) have no significant effect on CYP2D, while the activites of CYP2D increased 1.71, 1.97 and 2.89 times comparing to the control group. At the same time, borneol (300 mg·kg-1·d-1) caused the Cmax decreased 10.6% (P >0.05), AUC0-∞ decreased 27.5% (P<0.01), CL/F increased 41.1% (P<0.01), Vz/F increased 23.1% (P >0.05) of dextromethorphan. Our data provided that borneol speed up dextromethorphan's elimination in vivo. Since the activity of CYP2D can be induced by borneol, the metabolic interactions might happen when borneol and the substrate drug CYP2D are used together.

     

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