抑制25抗结核药物的潜力CYP活动在人类肝脏微粒体。

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Shimokawa Y,尤达N,近藤年代,Yamamura Y, Y Takiguchi Umehara K

抑制25抗结核药物的潜力CYP活动在人类肝脏微粒体。

生物制药公牛。2015;38 (9):1425 - 9。doi: 10.1248 / bpb.b15 - 00313。Epub 2015 6月20。

PubMed ID

26094899 (在PubMed

]

文摘

25的直接抑制潜在抗结核药物八CYP-specific反应在人类肝微粒体研究预测体内药物之间的相互作用(ddi)体外数据。利福平、利福和氨硫脲抑制一个CYP的反应。异烟肼和氯法齐明抑制性影响四个CYP反应,rifapentine、乙硫异烟胺,prothionamide广泛抑制CYP的反应。基于抑制常数(Ki)和治疗总抑制剂浓度[我]最大的八人血浆中药物,[我]max / Ki值计算评估临床ddi。[我]max / Ki值是0.20或更少对利福平、利福,和氨硫脲;0.15 - -2.0异烟肼;rifapentine 0.14 - -1.5;0.29 - -1.4乙硫异烟胺;prothionamide 0.41 - -2.2;氯法齐明-6.3和0.12。 The highest [I]max/Ki values were 2.0 for isoniazid on CYP3A4 [testosterone (T)]; 1.5 for rifapentine on CYP3A4 [midazolam (M)]; 1.4 for ethionamide on CYP2C8; 2.2, 1.8, and 1.3 for prothionamide on CYP2B6, CYP2C19, and CYP2C8, respectively; and 6.3 and 5.7 for clofazimine on CYP3A4 (M) and CYP3A4 (T), respectively. These drugs with high [I]max/Ki values lead to clinical DDIs. Considering the drug regimens for tuberculosis (TB) and co-infection with TB and human immunodeficiency virus, the inhibitory potential for CYP3A4 and CYP2B6 is particularly important. These results suggest that clofazimine and prothionamide are likely to cause clinically relevant DDIs when co-administered with products metabolized by CYP3A4 and CYP2B6, respectively. Isoniazid and rifapentine may cause DDIs with drugs metabolized by CYP3A4.

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
Rifapentine	细胞色素P450 2 c8	蛋白质	人类	未知的	诱导物	细节
Rifapentine	细胞色素P450 3 a4	蛋白质	人类	未知的	底物 诱导物	细节