The enhancement of cardiac toxicity by concomitant administration of Berberine and macrolides.
The enhancement of cardiac toxicity by concomitant administration of Berberine and macrolides.
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小檗碱和大环内酯类药物联合用药会增强心脏毒性。
DOI：
10.1016/j.ejps.2015.05.009
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发表时间：
2015-08
影响因子：
4.6
通讯作者：
李宝馨
中科院分区：
文献类型：
--
作者：
智多;冯攀峰;孙嘉亮;郭峰峰;张瑞;赵鑫;李宝馨
众所周知，hERG在心脏动作电位的III相复极化中起重要作用。hERG通道阻断可导致LQTS。抑制CYP代谢活性可使血浆浓度升高，进一步增加药物在心脏的蓄积。然而，升高的血清水平可能引起意外的毒性。因此，hERG和hERG的抑制试验是临床前研究的核心，因为它们可能导致严重的心脏毒性。黄连素是一种广泛使用的抗菌药物，常与大环内酯类药物合用治疗胃病。我们的目的是评估联合使用黄连素与大环内酯类药物的心脏毒性。(1)阿奇霉素通过加速通道失活降低hERG电流。(2)小檗碱与阿奇霉素的组合降低了hERG电流，由于对失活开始的高结合亲和力，产生比单独使用单一药物更强的抑制作用。(3)当细胞与小檗碱和克拉霉素同时灌注时，它们通过降低失活开始的时间常数对hERG电流表现出更强的抑制作用。(4)黄连素与克拉霉素联合用药对CYP3A活性的抑制作用强于单独用药。总的来说，这些结果表明，由于潜在的药物毒性，特别是心脏毒性，黄连素与大环内酯类药物合并使用可能需要密切监测。
As is well-known, hERG plays an essential role in phase III repolarization of cardiac action potentials. Blocking of hERG channels can lead to LQTS. Inhibition of the metabolism of CYPs activities may elevate plasma levels, to further increase accumulation of drug on cardiac. The elevated serum levels may however elicit unexpected toxicities. Therefore, the inhibition tests of hERG and CYP are central to the preclinical studies because they may lead to severe cardiac toxicity. Berberine is widely used as an antibacterial agent and often combined with macrolides to treat gastropathy. Our objective was to assess cardiac toxicity during the combined use of Berberine with macrolides. (1) Azithromycin reduced hERG currents by accelerated channel inactivation. (2) The combination of Berberine with Azithromycin reduced hERG currents, producing an inhibitive effect stronger than use of a single drug alone, due to the high binding affinity for the onset of inactivation. (3) When cells were perfused concomitantly with Berberine and Clarithromycin, they showed a stronger inhibitive effect on hERG currents by decreasing the time constant for the onset of inactivation. (4) The combined administration of Berberine with Clarithromycin had a powerful inhibitive effect on CYP3A activities than use of a single drug alone. Collectively, these results demonstrated that concomitant use of Berberine with macrolides may require close monitoring because of potential drug toxicities, especially cardiac toxicity.
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小檗碱对心肌细胞IK1、IK、HERG通道的抑制作用
影响因子：
8.2
作者：
李宝馨;杨宝峰;周晋;徐长庆;李玉荣
通讯作者：
李玉荣
DOI：
10.1124/jpet.113.209643
发表时间：
2014-02
期刊：
The Journal of Pharmacology and Experimental Therapeutics
影响因子：
--
作者：
P. Thurner;A. Stary-Weinzinger;Hend Gafar;V. Gawali;O. Kudlacek;Juergen Zezula;K. Hilber;S. Boehm;W. Sandtner;Xaver Koenig
通讯作者：
P. Thurner;A. Stary-Weinzinger;Hend Gafar;V. Gawali;O. Kudlacek;Juergen Zezula;K. Hilber;S. Boehm;W. Sandtner;Xaver Koenig
DOI：
10.1007/s00210-004-0952-3
发表时间：
2004-07
期刊：
Naunyn-Schmiedeberg's Archives of Pharmacology
影响因子：
--
作者：
E. Zitron;Claudia Kiesecker;E. Scholz;Sonja Lück;Ramona Bloehs;S. Kathöfer;Dierk Thomas;J. Kiehn;V. Kreye;H. Katus;W. Schoels;C. Karle
通讯作者：
E. Zitron;Claudia Kiesecker;E. Scholz;Sonja Lück;Ramona Bloehs;S. Kathöfer;Dierk Thomas;J. Kiehn;V. Kreye;H. Katus;W. Schoels;C. Karle
影响因子：
3
作者：
Aldo A. Rodríguez-Menchaca;Tania Ferrer-Villada;Jesus Lara;David Fernandez;R. Navarro-Polanco;J. Sánchez-Chapula
通讯作者：
Aldo A. Rodríguez-Menchaca;Tania Ferrer-Villada;Jesus Lara;David Fernandez;R. Navarro-Polanco;J. Sánchez-Chapula
影响因子：
2.7
作者：
Yun, Jun;Han, Minsoo;Hahn, Hoh-Gyu
通讯作者：
Hahn, Hoh-Gyu