肝病对药代动力学的影响。一个更新。

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Rodighiero V

肝病对药代动力学的影响。一个更新。

临床药典杂志1999 11月;37(5):399-431。

PubMed ID

10589374 (PubMed视图

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摘要

肝脏疾病可改变肝脏生物转化药物的动力学。本文综述了细胞色素P450 (CYP)在这一领域的最新进展。CYP是临床药理学中一个迅速发展的领域。近年来，有关药物代谢的特定异构体的信息有了极大的增加，但知识仍然不完整。关于肝病对特定CYP同工酶的影响的研究表明，某些同工酶比其他同工酶更容易受到肝病的影响。详细了解参与药物代谢的特定同工酶以及肝脏疾病对该酶的影响，可为肝功能损害患者调整剂量提供合理依据。肝脏代谢药物的能力取决于肝血流量和肝酶活性，这两者都可能受到肝病的影响。此外，肝功能衰竭可影响药物与血浆蛋白的结合。这些变化可以单独发生，也可以同时发生;当它们共存时，它们对药物动力学的影响是协同的，而不是简单的相加。 The kinetics of drugs with a low hepatic extraction are sensitive to hepatic failure rather than to liver blood flow changes, but drugs having a significant first-pass effect are sensitive to alterations in hepatic blood flow. The drugs examined in this review are: cardiovascular agents (angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, calcium antagonists, ketanserin, antiarrhythmics and hypolipidaemics), diuretics (torasemide), psychoactive and anticonvulsant agents (benzodiazepines, flumazenil, antidepressants and tiagabine), antiemetics (metoclopramide and serotonin antagonists), antiulcers (acid pump inhibitors), anti-infectives and antiretroviral agents (grepafloxacin, ornidazole, pefloxacin, stavudine and zidovudine), immunosuppressants (cyclosporin and tacrolimus), naltrexone, tolcapone and toremifene. According to the available data, the kinetics of many drugs are altered by liver disease to an extent that requires dosage adjustment; the problem is to quantify the required changes. Obviously, this requires the evaluation of the degree of hepatic impairment. At present there is no satisfactory test that gives a quantitative measure of liver function and its impairment. A critical evaluation of these methods is provided. Guidelines providing a rational basis for dosage adjustment are illustrated. Finally, it is important to consider that liver disease not only affects pharmacokinetics but also pharmacodynamics. This review also examines drugs with altered pharmacodynamics.

引用本文的药物库数据

药物酶

药物	酶	种类	生物	药理作用	行动
Garenoxacin	细胞色素P450 1A2	蛋白质	人类	没有	抑制剂	细节
Grepafloxacin	细胞色素P450 1A2	蛋白质	人类	未知的	底物 抑制剂	细节