环丙沙星大大增加浓度和低血压患者的影响tizanidine通过抑制其细胞色素P450 1 a2-mediated presystemic新陈代谢。

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Granfors MT、后方JT Neuvonen M, Neuvonen PJ

环丙沙星大大增加浓度和低血压患者的影响tizanidine通过抑制其细胞色素P450 1 a2-mediated presystemic新陈代谢。

中国新药杂志。2004年12月,76 (6):598 - 606。doi: 10.1016 / j.clpt.2004.08.018。

PubMed ID

15592331 (在PubMed

]

文摘

背景和目的:Tizanidine,中央骨骼肌肉松弛剂,是代谢主要由细胞色素P450 (CYP) 1 a2和口服生物利用度低。氟喹诺酮类抗生素环丙沙星只是适度CYP1A2的有效抑制剂。我们的目标是研究的程度和可能的互动机制与tizanidine环丙沙星。方法:在一个双盲、随机、二段式交叉研究中,10个健康志愿者摄入500毫克或安慰剂环丙沙星连续3天每天两次。3天,一剂4毫克tizanidine摄取1小时后早晨剂量的环丙沙星。等离子体浓度tizanidine和环丙沙星和药效学变量测量。咖啡因测试是用来标记CYP1A2活性。结果:环丙沙星增加血浆浓度时间曲线下的面积从0到无穷大(AUC (0-infinity)) tizanidine的10倍(范围、留学生和采样;P <措施)和峰值浓度的7倍(21-fold范围,4倍;P <措施),而其消除半衰期只有长时间从1.5到1.8小时(P = .007)。 The pharmacodynamic effects of tizanidine were much stronger during the ciprofloxacin phase than during the placebo phase with regard to changes in systolic blood pressure (-35 mm Hg versus -15 mm Hg, P = .001), diastolic blood pressure (-24 mm Hg versus -11 mm Hg, P < .001), Digit Symbol Substitution Test (P = .02), subjective drug effect (P = .002), and subjective drowsiness (P = .009). The AUC(0-infinity) of tizanidine and its change correlated (P < .01) with the caffeine/paraxanthine ratio and its change. CONCLUSIONS: Ciprofloxacin greatly elevates plasma concentrations of tizanidine and dangerously potentiates its hypotensive and sedative effects, mainly by inhibiting its CYP1A2-mediated metabolism, at least when administered 1 hour before tizanidine. Tizanidine seems to be a useful probe drug for measuring presystemic metabolism by CYP1A2. Care should be exercised when tizanidine is used concomitantly with ciprofloxacin.

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
环丙沙星	细胞色素P450 1 a2	蛋白质	人类	未知的	抑制剂	细节