与CYP3A4相互作用的药物对餐用葡萄糖调节剂瑞格列奈药代动力学、药效学和安全性的影响
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哈托普V，汉森KT，汤姆森MS
与CYP3A4相互作用的药物对餐用葡萄糖调节剂瑞格列奈药代动力学、药效学和安全性的影响
临床药学杂志。2003 6;43(6):649-60。
- PubMed ID
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12817528 (在PubMed］
- 摘要
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本研究的目的是分析瑞格列奈(一种短效胰岛素促分泌剂)和其他五种与CYP3A4相互作用的药物之间的相互作用:酮康唑、利福平、炔雌醇/左炔诺孕酮(口服避孕药)、辛伐他汀和硝苯地平。在两项开放标签、两期、随机交叉研究中，健康受试者单独接受瑞格列奈，酮康唑治疗第5天接受瑞格列奈，利福平治疗第7天接受瑞格列奈。在三项开放标签、三期、随机交叉研究中，健康受试者单独接受5天的瑞格列奈治疗;单独服用乙炔雌二醇/左炔诺孕酮、辛伐他汀或硝苯地平5天;或服用5天瑞格列奈，同时服用炔雌醇/左炔诺孕酮、辛伐他汀或硝苯地平。与单独应用瑞格列奈相比，同时使用酮康唑可使瑞格列奈的平均AUC0-infinity增加15%，平均Cmax增加7%。利福平同时使瑞格列奈的平均AUC0-infinity降低31%，平均Cmax降低26%。与CYP3A4底物同时治疗的瑞格列奈的平均AUC0-5 h和平均Cmax改变了1%和17%(炔雌醇/左炔诺孕酮)，2%和27%(辛伐他汀)，或11%和3%(硝苯地平)。瑞格列奈给药后，酮康唑和利福平的血糖浓度变化小于8%。在所有五项研究中，大多数不良事件都与低血糖有关，这与服用血糖调节剂的正常人群所预期的一样。 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.
引用本文的药库数据
- 药物酶
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药物 酶 种类 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
软件中的交互Repaglinide 酮康唑 瑞格列奈与酮康唑合用可提高血清浓度。
