CYP3A4抑制剂的影响红霉素药物动力学的利多卡因及其与正常受试者的药物活性代谢物和肝功能受损。
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奥兰多R, Piccoli P·德·马丁,Padrini R,使P
CYP3A4抑制剂的影响红霉素药物动力学的利多卡因及其与正常受试者的药物活性代谢物和肝功能受损。
Br中国新药杂志。2003年1月;55 (1):86 - 93。
- PubMed ID
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12534644 (在PubMed]
- 文摘
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目的:本研究的目的是:(i)评估的影响细胞色素P450 (CYP) 3 a4抑制剂,红霉素,静脉注射利多卡因和它的两个药物动力学的药物活性代谢物,monoethylglycinexylidide (MEGX)和glycinexylidide (GX);(2)评估是否影响红霉素的抑制作用在利多卡因间隙和MEGX肝功能测试的结果取决于肝脏功能状态;和(3)确定的影响中度和重度肝功能异常处理动力学利多卡因。方法:这项研究是进行10个健康的志愿者,和10孩子的A类和C类肝硬化患者,根据一项双盲、随机、双向交叉设计。第一天的调查,所有受试者接受三个口服剂量红霉素(600毫克的ethylsuccinate酯)或安慰剂,和两个进一步剂量2天。一个小时后第四剂量,受试者被要求在1毫克公斤利多卡因静脉注射。定时测定血浆样本然后获得直到12 h浓度的利多卡因,MEGX和GX。结果:红霉素引起显著,尽管有限,利多卡因和MEGX药代动力学参数的修改。在健康的志愿者,利多卡因间隙减少从9.93到8.15毫升公斤最低为1(平均百分比比(95% CI)、82(65 - 98)],半衰期长时间从2.23到02.80 h(平均百分比比(95% CI)、130 (109 - 151)];MEGX面积曲线从0 h - 12 h从665提高到886 ng ml-1 h(平均百分比比(95% CI)、129 (102 - 156)]。 Quantitatively similar modifications were observed in the two cirrhotic groups. GX concentrations were lowered in all study groups, although not to statistically significant extents. Erythromycin coadministration caused no appreciable interference with the results of the MEGX test. Only in patients with Child's grade C liver cirrhosis were lignocaine kinetic parameters significantly altered with respect to healthy volunteers. Thus, clearance was approximately halved, steady-state volume of distribution was increased, and terminal half-life was more than doubled. CONCLUSIONS: Although erythromycin only modestly decreases lignocaine clearance, it causes a concomitant elevation of the concentrations of its pharmacologically active metabolite MEGX. A pharmacodynamic study following lignocaine infusion to steady state appears necessary to assess the actual clinical relevance of these combined effects. The degree of liver dysfunction has no influence on the extent of the erythromycin-lignocaine interaction, whereas it markedly influences the extent of the changes in lignocaine pharmacokinetics. These findings indicate that no dose adjustment is needed in patients with moderate liver cirrhosis, whereas the lignocaine dose should be halved in patients with severe cirrhosis.
DrugBank数据引用了这篇文章
- 药物酶
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药物 酶 类 生物 药理作用 行动 红霉素 细胞色素P450 3 a4 蛋白质 人类 没有底物抑制剂细节 - 药物的相互作用Learn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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药物 交互 整合药物之间
在您的软件的交互Dronedarone 红霉素 的血清浓度Dronedarone时可以增加结合红霉素。 红霉素 氟康唑 氟康唑可能提高红霉素的QTc-prolonging arrhythmogenic活动。
