多个人工细胞色素导致右美沙芬体外生物转化:CYP2C9的作用,CYP2C19、CYP2D6、CYP3A。

文章的细节

引用

复制到剪贴板

冯·Moltke LL格林布拉特DJ,格拉希JM,奶奶BW, Venkatakrishnan K,施密德J, Harmatz JS,材质RI

多个人工细胞色素导致右美沙芬体外生物转化:CYP2C9的作用,CYP2C19、CYP2D6、CYP3A。

J制药药物杂志。1998年9月,50 (9):997 - 1004。doi: 10.1111 / j.2042-7158.1998.tb06914.x。

PubMed ID

9811160 (在PubMed

]

文摘

细胞色素调停的生物转化右美沙芬dextrorphan 3-methoxymorphinan,其主要代谢产物在人,研究了利用肝微粒体和微粒体包含个人cDNA-transfected人类lymphoblastoid细胞表达的细胞色素。由肝微粒体体外形成dextrorphan右美沙芬介导的高亲和性酶主要由(公里(底物浓度产生最大反应速度)3-13 microM)。形成dextrorphan 25 microM右美沙芬强烈抑制了奎尼丁(IC50(抑制浓度导致50%)= 0.37 microM);抑制sulphaphenazole大约是18%和奥美拉唑,酮康唑有微小的影响。Dextrorphan形成的微粒体从右美沙芬cDNA-transfected lymphoblastoid细胞表达CYP2C9 2 c19,和2 d6但不是由那些表达CYP1A2, 2 e1或3 a4。尽管CYP2D6体内大量的低,这个细胞色素酶被确认为主导调停dextrorphan形成在衬底浓度低于10 microM。形成从右美沙芬3-methoxy-morphinan肝微粒体平均259公里microM。形成3-methoxymorphinan 25 microM右美沙芬酮康唑的IC50 1.15 microM;sulphaphenazole、奥美拉唑和奎尼丁几乎没有影响。3-Methoxymorphinan是由微粒体从cDNA-transfected lymphoblastoid细胞表达CYP2C9 2 c19 2 d6,和3 a4,但不是由那些表达CYP1A2或2 e1。 CYP2C19 had the highest affinity (Km = 49 microM) whereas CYP3A4 had the lowest (Km = 1155 microM). Relative abundances of the four cytochromes were determined in liver microsomes by use of the relative activity factor approach. After adjustment for relative abundance, CYP3A4 was identified as the dominant enzyme mediating 3-methoxymorphinan formation from dextromethorphan, although CYP2C9 and -2C19 were estimated to contribute to 3-methoxymorphinan formation, particularly at low substrate concentrations. Although formation of dextrorphan from dextromethorphan appears to be sufficiently specific to be used as an in-vitro or in-vivo index reaction for profiling of CYP2D6 activity, the findings raise questions about the specificity of 3-methoxymorphinan formation as an index of CYP3A activity.

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
右美沙芬	细胞色素P450 2 c19	蛋白质	人类	未知的	底物	细节
右美沙芬	细胞色素P450 2 c9	蛋白质	人类	未知的	底物	细节