Human liver aldehyde oxidase: Inhibition by 239 drugs
Human liver aldehyde oxidase: Inhibition by 239 drugs
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DOI：
10.1177/0091270003260336
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发表时间：
2004-01-01
影响因子：
2.9
通讯作者：
Beedham, C
中科院分区：
文献类型：
--
作者：
Obach, RS;Huynh, P;Beedham, C
作者测试了239种常用药物和其他化合物，以抑制人类肝细胞质中药物代谢酶——醛氧化酶的潜力。建立了一种灵敏、中等通量的高效液相色谱-质谱法测定邻苯二嗪氧化醛氧化酶催化产物1-酞嗪酮。研究了239种药物和其他感兴趣的化合物在50mum的浓度下对该活性的抑制作用。其中，选择性雌激素受体调节剂雷洛昔芬（IC50 = 2.9 nM）、他莫昔芬、雌二醇和乙炔雌二醇也是有效的抑制剂。其他具有醛氧化酶抑制作用的药物包括吩噻嗪类、三环抗抑郁药、三环非典型抗精神病药和二氢吡啶类钙通道阻滞剂，以及其他一些药物，包括氯雷他定、环苯扎林、阿莫地喹、马普替林、昂丹西琼、普罗帕酮、多潘立酮、喹阿卡因、酮康唑、异拉帕米、他克林和沙美特罗。这些发现讨论了这些药物与醛氧化酶参与代谢的药物之间可能存在的潜在药物相互作用，并对醛氧化酶抑制介导的临床药物相互作用的可能性进行了调查。(C) 2004年美国临床药理学学会。
The authors tested 239 frequently used drugs and other compounds for their potential to inhibit the drug-metabolizing enzyme, aldehyde oxidase, in human liver cytosol. A sensitive, moderate throughput HPLC-MS assay was developed for 1-phthalazinone, the aldehyde oxidase-catalyzed product of phthalazine oxidation. Inhibition of this activity was examined for the 239 drugs and other compounds of interest at a test concentration of 50 muM. Thirty-six compounds exhibited greater than 80% inhibition and were further examined for measurement of IC50, The most potent inhibitor observed was the selective estrogen receptor modulator, raloxifene (IC50 = 2.9 nM), and tamoxifen, estradiol, and ethinyl estradiol were also potent inhibitors. Other classes of drugs that demonstrated inhibition of aldehyde oxidase included phenothiazines, tricyclic antidepressants, tricyclic atypical antipsychotic agents, and dihydropyridine calcium channel blockers, along with some other drugs, including loratadine, cyclobenzaprine, amodiaquine, maprotiline, ondansetron, propafenone, domperidone, quinacrine, ketoconazole, verapamil, tacrine, and salmeterol. These findings are discussed in context to potential drug interactions that could be observed between these agents and drugs for which aldehyde oxidase is involved in metabolism and warrant investigation of the possibility of clinical drug interactions mediated by inhibition of this enzyme. (C) 2004 the American College of Clinical Pharmacology.