Xenobiotic metabolism: the effect of acute kidney injury on non-renal drug clearance and hepatic drug metabolism.
Xenobiotic metabolism: the effect of acute kidney injury on non-renal drug clearance and hepatic drug metabolism.
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DOI：
10.3390/ijms15022538
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发表时间：
2014-02-13
影响因子：
5.6
通讯作者：
Philips B
中科院分区：
文献类型：
--
作者：
Dixon J;Lane K;Macphee I;Philips B
急性肾损伤（阿基）是危重病的常见并发症，有证据表明阿基会破坏其他器官的功能。慢性肾脏疾病（CKD）患者通过细胞色素P450（CYP）酶组降低了药物的肝脏代谢，这是一种公认的现象，阿基的药物给药指南通常是从CKD患者获得的数据推断的。然而，这种方法是有缺陷的，因为阿基中存在几个混杂因素。来自调查阿基对肝脏活性影响的动物研究的数据是相互矛盾的，尽管大多数结果确实表明阿基损害肝脏活性。最近，人类研究数据也表明与阿基相关的CYP3A活性降低，特别是CYP3A亚型。此外，初步数据表明，与编码非功能性蛋白质的变体CYP3A5*3纯合子患者相比，表达功能性等位基因变体CYP3A5*1的患者可能受到保护，免受阿基的有害影响。总之，有必要使药物处方个性化，特别是对病情较重和脆弱的患者，但这需要更深入地探讨。
Acute kidney injury (AKI) is a common complication of critical illness, and evidence is emerging that suggests AKI disrupts the function of other organs. It is a recognized phenomenon that patients with chronic kidney disease (CKD) have reduced hepatic metabolism of drugs, via the cytochrome P450 (CYP) enzyme group, and drug dosing guidelines in AKI are often extrapolated from data obtained from patients with CKD. This approach, however, is flawed because several confounding factors exist in AKI. The data from animal studies investigating the effects of AKI on CYP activity are conflicting, although the results of the majority do suggest that AKI impairs hepatic CYP activity. More recently, human study data have also demonstrated decreased CYP activity associated with AKI, in particular the CYP3A subtypes. Furthermore, preliminary data suggest that patients expressing the functional allele variant CYP3A5*1 may be protected from the deleterious effects of AKI when compared with patients homozygous for the variant CYP3A5*3, which codes for a non-functional protein. In conclusion, there is a need to individualize drug prescribing, particularly for the more sick and vulnerable patients, but this needs to be explored in greater depth.
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影响因子：
4.3
作者：
Dreisbach AW;Lertora JJ
通讯作者：
Lertora JJ
影响因子：
13.2
作者：
Abosaif, NY;Tolba, YA;El Nahas, AM
通讯作者：
El Nahas, AM
影响因子：
13.6
作者：
Doi, Kent;Yuen, Peter S. T.;Star, Robert A.
通讯作者：
Star, Robert A.
影响因子：
38.9
作者：
HEINEMEYER, G;LINK, J;ROOTS, I
通讯作者：
ROOTS, I
影响因子：
19.6
作者：
Golab, Fereshteh;Kadkhodaee, Mehri;Soleimani, Manoocher
通讯作者：
Soleimani, Manoocher