与CYP3A4交互影响的药物药物动力学、药效学和安全性的膳食血糖调节repaglinide。
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Hatorp V,汉森KT,汤姆森女士
与CYP3A4交互影响的药物药物动力学、药效学和安全性的膳食血糖调节repaglinide。
中国新药杂志。2003年6月,43 (6):649 - 60。
- PubMed ID
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12817528 (在PubMed]
- 文摘
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本研究的目的是分析药物之间的相互作用repaglinide,短效胰岛素促分泌素,和五个其他药物相互作用CYP3A4:酮康唑、利福平、ethinyloestradiol / levonorgestrel(一种口服避孕药),辛伐他汀和硝苯地平。在两个非盲、两期,随机交叉研究,健康受试者仅接受repaglinide, repaglinide酮康唑治疗5天,7天或repaglinide的利福平治疗。在三时期,三个非盲、随机交叉研究,健康受试者仅接受repaglinide 5天;5天的ethinyloestradiol / levonorgestrel、辛伐他汀或单独硝苯地平;或5天的repaglinide伴随ethinyloestradiol / levonorgestrel,辛伐他汀、硝苯地平。独自repaglinide管理相比,伴随的酮康唑对repaglinide AUC0-infinity意味着增加了15%,意味着Cmax 7%。伴随的利福平下降意味着AUC0-infinity repaglinide 31%,意味着Cmax 26%。伴随治疗CYP3A4基质改变意味着AUC0-5 h和意味着Cmax repaglinide (ethinyloestradiol / levonorgestrel) 1%, 17%, 2%和27%(辛伐他汀),或11%和3%(硝苯地平)。后的血糖浓度repaglinide剂量改变了不到8%酮康唑和利福平。在所有五个研究,大多数不良事件相关的低血糖,预计在一个正常的人口血糖调节剂。 The safety profile of repaglinide was not altered by pretreatment with ketoconazole or rifampicin or by coadministration with ethinyloestradiol/levonorgestrel. The incidence of adverse events increased with coadministration of simvastatin or nifedipine compared to either repaglinide or simvastatin/nifedipine treatment alone. No clinically relevant pharmacokinetic interactions occurred between repaglinide and the CYP3A4 substrates ethinyloestradiol/levonorgestrel, simvastatin, or nifedipine. The pharmacokinetic profile of repaglinide was altered by administration of potent inhibitors or inducers, such as ketoconazole or rifampicin, but to a lesser degree than expected. These results are probably explained by the metabolic pathway of repaglinide that involves other enzymes than CYP3A4, reflected to some extent by a small change in repaglinide pharmacodynamics. Thus, careful monitoring of blood glucose in repaglinide-treated patients receiving strong inhibitors or inducers of CYP3A4 is recommended, and an increase in repaglinide dose may be necessary. No safety concerns were observed, except a higher incidence in adverse events in patients receiving repaglinide and simvastatin or nifedipine.
beplay体育安全吗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 Levonorgestrel 细胞色素P450 3 a4 蛋白质 人类 未知的底物细节 - 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Repaglinide 酮康唑 的血清浓度Repaglinide时可以增加与酮康唑相结合。
