833年的多药耐药性调制器valspodar (PSC)是由人类细胞色素P450 3代谢。影响药物之间的相互作用和药理作用的主要代谢物。

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费舍尔V, Rodriguez-Gascon Heitz F,泰恩R·豪C,科恩D,维氏AE

833年的多药耐药性调制器valspodar (PSC)是由人类细胞色素P450 3代谢。影响药物之间的相互作用和药理作用的主要代谢物。

药物金属底座Dispos。1998年8月,26(8):802 - 11所示。

PubMed ID

9698296 (在PubMed

]

文摘

的新陈代谢valspodar (PSC 833;PSC),开发多种resistance-reversing代理,调查评估潜在的药物之间的相互作用和药理作用的主要代谢物。PSC的主要代谢产物所产生的人类肝脏微粒体monohydroxylated,揭示了LC / MS。羟基化的主要网站在氨基酸,导致M9,由共同色谱分析与合成M9。二羟和N-demethylated代谢物也被检测到。PSC两人类肝脏代谢公里值的1.3 - -2.8 microM展出。内在是9-36毫升/分钟/公斤的体重。PSC生物转化细胞色素P450 (CYP或P450) 3是一个依赖,基于化学抑制和中国仓鼠卵巢细胞表达CYP3A的新陈代谢。酮康唑是一个竞争性抑制剂(Ki microM -0.04 = 0.01)。抑制了27个化合物,其中包括四个抗肿瘤的药物,与这些化合物对CYP3A的抑制性潜力。 For vinblastine, paclitaxel, doxorubicin, and etoposide, the IC50 values were 5, 12, 20, and 150 microM, respectively. M9 was also an inhibitor, with a lower apparent affinity for CYP3A (IC50 = 21 microM), compared with that of PSC. M9 was also less active as a multidrug resistance-reversing agent. M9 demonstrated low potency in sensitizing resistant cells to paclitaxel and was a poor inhibitor of rhodamine-123 efflux from paclitaxel-resistant cells. In addition, compared with PSC, a higher concentration of M9 was needed to compete with the photoaffinity labeling of P-glycoprotein. Conversely, PSC inhibited only reactions catalyzed by CYP3A, including cyclosporine A metabolism (IC50 = 6.5 microM) and p-hydroxyphenyl-C3'-paclitaxel formation (Ki = 1.2 microM). Thus, PSC behaves in a manner very similar to that of other cyclosporines, and a comparable drug-drug interaction profile is expected.

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
紫杉醇	细胞色素P450 3 a4	蛋白质	人类	未知的	底物 诱导物	细节