Measuring altered disposition of xenobiotics in experimental models of liver disease.
Measuring altered disposition of xenobiotics in experimental models of liver disease.
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DOI：
10.1002/0471140856.tx2301s52
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发表时间：
2012-05-01
期刊：
影响因子：
--
通讯作者：
Cherrington, Nathan J
中科院分区：
文献类型：
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作者：
Hardwick, Rhiannon N;Cherrington, Nathan J
了解控制化合物处置的代谢途径和排泄机制对于安全使用药物制剂至关重要。由于肝脏是负责代谢和消除外源性物质的主要器官，因此慢性肝病可由于药物代谢酶和转运蛋白的表达或功能的变化而对许多外源性物质的处置产生显著影响。肝脏疾病可导致体内异生物质的保留增加，导致个体更多地暴露于潜在有害的化合物，这可能导致毒性。另一方面，肝脏疾病也可能上调异生物质的消除过程，加速其从体内清除。对于药物，消除增强可能导致药理作用降低。这种改变可能需要调整剂量以实现所需的治疗结果。
Understanding the metabolic pathway and excretion mechanisms governing the disposition of a compound is essential to the safe use of pharmaceutical agents. Because the liver is the primary organ responsible for the metabolism and elimination of xenobiotics, chronic liver disease can have a significant effect on the disposition of many xenobiotics due to changes in the expression or function of drug metabolizing enzymes and transporters. Liver disease can result in increased retention of a xenobiotic within the body, causing greater exposure of the individual to a potentially harmful compound, which may lead to toxicity. On the other hand, liver disease may also up-regulate the elimination processes of a xenobiotic, accelerating its removal from the body. With regard to a pharmaceutical agent, enhanced elimination may result in a decreased pharmacologic effect. Such alterations may necessitate dosage adjustments to achieve the desired therapeutic outcome.