CYP2B6*6 or Not CYP2B6*6-That Remains a Question for Precision Medicine and Ketamine!
CYP2B6*6 or Not CYP2B6*6-That Remains a Question for Precision Medicine and Ketamine!
复制标题
CYP2B6*6 或不是 CYP2B6*6——这对于精准医学和氯胺酮来说仍然是一个问题！
DOI：
10.1097/aln.0000000000001399
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发表时间：
2016
期刊：
影响因子：
8.8
通讯作者：
Hakonarson,Hakon
中科院分区：
文献类型：
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作者：
Cook-Sather,ScottD;Adamson,PeterC;Li,Jin;Hakonarson,Hakon
虽然肯定不是哈姆雷特提出的可怕的生死存亡问题，但对CYP2B6和其他遗传位点变异的详细了解能否为氯胺酮的临床剂量带来精确的药物？我们相信它会的，但由于适应症、给药途径和其他因素的细微差别。在这一期的麻醉学中，Rao和他的同事介绍了他们在氯胺酮药物遗传学方面的工作，试图更好地理解药物反应差异的原因，从代谢和药代动力学差异开始。1细胞色素P450，家族2，B亚家族，成员6(CYP2B6)是一种高亲和力蛋白，被认为是氯胺酮分解代谢的主导者。CYP2B6的基因编码高度多态，常见的CYP2B6*6(516G>；T，785A>；G)变异主要存在于非洲裔人群中，与肝脏中CYP2B6表达减弱相关。在功能上，相关基因产物CYP2B6。6和肝微粒体在体外均表现为氯胺酮代谢降低。2此外，在接受100-500 mg/24 h氯胺酮皮下注射的慢性疼痛患者中，CYP2B6*6等位基因导致稳态氯胺酮清除量降低，并具有基因剂量效应。3.
While certainly not the dire existential question posed by Hamlet, could detailed knowledge of variants at CYP2B6 and other genetic loci bring precision medicine to the clinical dosing of ketamine? We believe that it will, but one nuanced by indication, route of administration, and other factors.In this issue of Anesthesiology, Rao and colleagues present their work on the pharmacogenetics of ketamine in an attempt to better understand the etiologies of drug response variability, beginning with metabolism and pharmacokinetic differences. 1 Cytochrome P450, family 2, subfamily B, member 6 (CYP2B6) is a high-affinity protein thought to predominate ketamine catabolism. The gene coding for CYP2B6 (CYP2B6) is highly polymorphic, with the common CYP2B6* 6 (516G> T, 785A> G) variant, found largely in those of African descent, correlating with diminished hepatic CYP2B6 expression. Functionally, the associated gene product CYP2B6. 6 and liver microsomes from CYP2B6* 6 carriers both show reduced ketamine metabolism in vitro. 2 Moreover, in chronic pain patients treated with 100–500 mg/24 h subcutaneous ketamine infusions, the CYP2B6* 6 allele confers reduced steady-state ketamine clearance with gene-dose effect. 3