利福平只是一个弱诱导物的CYP1A2-mediated presystemic和系统性新陈代谢:研究tizanidine和咖啡因。

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后方JT, Granfors MT Neuvonen PJ

利福平只是一个弱诱导物的CYP1A2-mediated presystemic和系统性新陈代谢:研究tizanidine和咖啡因。

欧元中国新药杂志。2006年6月,62 (6):451 - 61。doi: 10.1007 / s00228 - 006 - 0127 - x。Epub 2006年4月27日。

PubMed ID

16758262 (在PubMed

]

文摘

摘要目的:利福平大大减少了许多药物的血浆浓度。我们的目的是描述的可诱导性细胞色素P450 (CYP) 1 a2,利福平,使用tizanidine和咖啡因作为探针药物presystemic和系统性CYP1A2-mediated新陈代谢。方法:在一个随机,二段式交叉研究,十个健康志愿者都进行了5天预处理与每天600毫克利福平或安慰剂。6天,一个4 mg剂量tizanidine口服药物。血浆和尿液浓度的父tizanidine和几个代谢物(m3, M-4 M-5, M-9,打光最后一)和药效学变量测量24 h。咖啡因测试执行阶段。结果:利福平适度降低血浆浓度峰值(51%;P = 0.002)和血浆浓度时间曲线下面积(AUC (0-infinity)) (54%;父tizanidine P = 0.009),并没有影响其半衰期。tizanidine / m3和tizanidine / M-4 AUC (0-infinity)比率略(30%;P = 0.014; and by 38%; P = 0.007) decreased by rifampicin. Also, the excretion of metabolites M-3, M-4 and M-5 into urine was reduced (P < 0.005), but that of M-10 was increased (P = 0.008) by rifampicin. Rifampicin reduced the tizanidine/M-10 ratio (by 55%; P = 0.047) but had no significant effect on the other tizanidine/metabolite ratios in urine. The caffeine/paraxanthine ratio was reduced by 23% (P = 0.081) by rifampicin. The effect of rifampicin on the caffeine/paraxanthine ratio correlated significantly with the effect of rifampicin on, for example, the AUC(0-infinity) of tizanidine and the tizanidine/M-3 AUC(0-infinity) ratio. The pharmacodynamic effects of tizanidine were reduced by rifampicin. CONCLUSIONS: Rifampicin moderately decreases the plasma concentrations of tizanidine. The strong inducing effects of rifampicin on other CYP enzymes, e.g. CYP3A4, may have contributed to the findings, and the inducibility of CYP1A2-mediated presystemic (tizanidine) and systemic (tizanidine, caffeine) metabolism by rifampicin is weak at the most. Compared to CYP3A4 substrate drugs, substrates of CYP1A2 are much less susceptible to drug interactions caused by enzyme inducers of the rifampicin type.

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药物酶

药物	酶	类	生物	药理作用	行动
利福平	细胞色素P450 1 a2	蛋白质	人类	未知的	诱导物	细节