用鸡尾酒法评估香菇多糖对大鼠细胞色素P450活性的影响。
Evaluation of lentinan effects on cytochrome P450 activity in rats by a cocktail method.
作者信息
Lin Yiping, Wei Yanli, Hu Xiaoxia, Wu Meiling, Yao Jingchan, Ying Xiaoqian, Fu Xiaoyan, Ding Mingxing, Qiao Liman
机构信息
Jinhua Polytechnic, Jinhua 321007, Zhejiang, China.
Jinhua Central Hospital, Jinhua 321000, Zhejiang, China.
出版信息
Iran J Basic Med Sci. 2019 Mar;22(3):296-301. doi: 10.22038/ijbms.2019.31611.7611.
OBJECTIVES
In this study, a cocktail of probe drugs was used to assess whether lentinan could influence the activities of rat enzymes CYP3A4, CYP2D6, CYP1A2, CYP2C19, and CYP2C9 in vivo.
MATERIALS AND METHODS
Fourteen days after intraperitoneal injection of lentinan, rats were given an oral dose of a cocktail solution containing phenacetin, tolbutamide, omeprazole, metoprolol, and midazolam. Then, we obtained blood in specific durations for the determination of plasma concentration of the probe drugs using UPLC-MS/MS. We also evaluated the pharmacokinetic parameters using the DAS 2.0 software.
RESULTS
We found that various concentrations of lentinan increased the activity of rat CYP1A2, CYP3A4, CYP2D6, and CYP2C19 but not CYP2C9.
CONCLUSION
These findings suggest that clinical application of lentinan combination with CYP3A4, CYP1A2, CYP2C19, or CYP2D6 should be given careful consideration as this may lead to herb-drug interactions and hence treatment failure.
目的
在本研究中，使用一组探针药物来评估香菇多糖是否能在体内影响大鼠的细胞色素P450 3A4（CYP3A4）、细胞色素P450 2D6（CYP2D6）、细胞色素P450 1A2（CYP1A2）、细胞色素P450 2C19（CYP2C19）和细胞色素P450 2C9（CYP2C9）酶的活性。
材料与方法
腹腔注射香菇多糖14天后，给大鼠口服一剂含有非那西丁、甲苯磺丁脲、奥美拉唑、美托洛尔和咪达唑仑的混合溶液。然后，在特定时间段采集血液，使用超高效液相色谱-串联质谱法（UPLC-MS/MS）测定探针药物的血浆浓度。我们还使用DAS 2.0软件评估药代动力学参数。
结果
我们发现不同浓度的香菇多糖增加了大鼠CYP1A2、CYP3A4、CYP2D6和CYP2C19的活性，但未增加CYP2C9的活性。
结论
这些发现表明，香菇多糖与CYP3A4、CYP1A2、CYP2C19或CYP2D6联合应用于临床时应谨慎考虑，因为这可能导致草药-药物相互作用，进而导致治疗失败。
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