摘要
目的:在人体内研究止咳橘红对CYP3A4和CYP1A2的抑制作用,以预测 止咳橘红与常用临床药物的相互作用。方法:咪哒唑仑和咖啡因分别作为CYP3A4和 CYP1A2的探针药物,采取交叉设计,10名受试者在服用3d止咳 橘红的前后均服用7.5mg咪哒唑仑和100mg咖啡因,服药后采血测定两者及 代谢产物的代谢动力学参数。探针药物及代谢物的浓度用HPLC-MS法测定,Cmax、tmax从药时曲线中直接读出,AUC用梯形法计算,Ke用3P87程序进行拟合计算,分析服药前后CYP3A4和CYP1A2被抑制的情况。结果服用止咳橘红后,咪哒唑仑的代谢受到了轻微的抑制,它的血药浓度、达峰时间和药时曲线下面积都有了升高趋势,但无显著差异。而咖啡因的代谢未受到影响。结论止咳橘红对CYP3A4的活性有较弱的抑制作用,能够导致CYP3A4底物咪哒唑仑代谢的轻微抑制,而对CYP1A2的活性没有影响。止咳橘红长期使用或超过治疗剂量使用时是否会对CYP3A4产生显著性影响,尚需进一步的研究证明。
OBJECTIVE: To evaluate the inhibit effect of Zhi-Ke-Ju-Hong on CYP3A4 and CYP1A2 activity in ten volunteers and to forecast the drug-drug interaction with it. METHOD: In ten healthy male volunteers, use two-way cross design, taking 7.5mg midazolam and 100mg caffeine before and after three days Zhi-Ke-Ju-Hong administration, blood samples were collected. Plasma concentration of midazolam, caffeine and their metabolites were determined by high-performance liquid chromatography-mass spectrometry (HPLC-MS). CYP3A4 and CYP1A2 activity and Pharmacokinetic parameters of probe drugs were compared before and after Zhi-Ke-Ju-Hong administration. RESULTS:The metabolism of midazolam was inhibited slightly by Zhi-Ke-Ju-Hong. CYP3 A4, Cmax, tmax and AUC were all increased after three days Zhi-Ke-Ju-Hong administration, but not significant. t1/2 was significantly increased by Zhi-Ke-Ju-Hong administration (P< 0.05). No influences on caffeine metabolism were observed. CONCLUSION: Zhi-Ke-Ju-Hong can affect midazolam metabolism slightly. The possible reason is that some compositions of Zhi-Ke-Ju-Hong have inhibited effect on CYP3A4. Zhi-Ke-Ju-Hong have no inhibit effect on CYP1A2.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2002年第3期215-218,共4页
The Chinese Journal of Clinical Pharmacology
