Pharmacokinetic-pharmacodynamic与β-还原酶抑制剂药物的相互作用。

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威廉姆斯D,费利J

Pharmacokinetic-pharmacodynamic与β-还原酶抑制剂药物的相互作用。

Pharmacokinet。2002; 41 (5): 343 - 70。doi: 10.2165 / 00003088-200241050-00003。

PubMed ID

12036392 (在PubMed

]

文摘

β-还原酶抑制剂(他汀类药物)是有效的在初级和二级预防缺血性心脏病。作为一个群体,这些药物耐受性良好,除了两个少见但潜在的严重副作用:海拔肝酶和骨骼肌异常,从良性肌痛到危及生命的横纹肌溶解。与他汀类药物副作用常常与药物的相互作用,因为它们在老年患者长期使用可能会暴露于复方用药。最近撤出cerivastatin死于横纹肌溶解的结果说明了这种相互作用的临床重要性。药物的相互作用涉及他汀类药物可能药效学和药代动力学基础上,或两者兼而有之。这些药物是高度提取的肝脏,位移相互作用有限的重要性。细胞色素P450 (CYP)酶系统中扮演一个重要的部分在他汀类药物的代谢,导致临床相关的交互与其他代理,特别是环孢菌素、红霉素、伊曲康唑、酮康唑和HIV蛋白酶抑制剂,也通过这种酶系统代谢。一个额外的复杂特性,不同个体的他汀类药物代谢不同的度,在某些情况下产生活性代谢物。CYP3A家族开始新陈代谢洛伐他汀,辛伐他汀、阿托伐他汀和cerivastatin,而CYP2C9开始新陈代谢fluvastatin。Cerivastatin也是由CYP2C8代谢。 Pravastatin is not significantly metabolised by the CYP system. In addition, the statins are substrates for P-glycoprotein, a drug transporter present in the small intestine that may influence their oral bioavailability. In clinical practice, the risk of a serious interaction causing myopathy is enhanced when statin metabolism is markedly inhibited. Thus, rhabdomyolysis has occurred following the coadministration of cyclosporin, a potent CYP3A4 and P-glycoprotein inhibitor, and lovastatin. Itraconazole has been shown to increase exposure to simvastatin and its active metabolite by at least 10-fold. Pharmacodynamically, there is an increased risk of myopathy when statins are coprescribed with fibrates or nicotinic acid. This occurs relatively infrequently, but is particularly associated with the combination of cerivastatin and gemfibrozil. Statins may also alter the concentrations of other drugs, such as warfarin or digoxin, leading to alterations in effect or a requirement for clinical monitoring. Knowledge of the pharmacokinetic properties of the statins should allow the avoidance of the majority of drug interactions. If concurrent therapy with known inhibitors of statin metabolism is necessary, the patient should be monitored for signs and symptoms of myopathy or rhabdomyolysis and the statin should be discontinued if necessary.

beplay体育安全吗DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
Midomafetamine	细胞色素P450 2 d6	蛋白质	人类	没有	底物	细节