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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Studies to investigate the pharmacokinetic interactions between ranolazine and ketoconazole, diltiazem, or simvastatin during combined administration in healthy subjects.
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Studies to investigate the pharmacokinetic interactions between ranolazine and ketoconazole, diltiazem, or simvastatin during combined administration in healthy subjects.

机译：研究在健康受试者中联合给药期间雷诺嗪与酮康唑，地尔硫卓或辛伐他汀之间的药代动力学相互作用的研究。

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摘要

The interactions of ranolazine, a new antianginal compound, with inhibitors and substrates of the CYP3A isoenzyme family were studied in 1 open-label and 4 double-blind, randomized, multiple-dose studies. In healthy adult volunteers, the authors sought (1) to determine the steady-state pharmacokinetics, safety, and tolerability of immediate- and sustained-release ranolazine with and without ketoconazole, diltiazem, or simvastatin and (2) to evaluate the effect of ranolazine on the pharmacokinetics of diltiazem, simvastatin, simvastatin metabolites, and HMG-CoA reductase activity. Ketoconazole increased ranolazine plasma concentrations and reduced the CYP3A4-mediated metabolic transformation of ranolazine, confirming that CYP3A4 is the primary metabolic pathway for ranolazine. Diltiazem reduced oral clearance of ranolazine in a dose-dependent manner. Simvastatin did not affect ranolazine pharmacokinetics, although ranolazine increased the AUC and C(max) of simvastatin, simvastatin acid, 2 simvastatin metabolites, and HMG-CoA reductase activity by <2-fold. Administration of ranolazine in combination with diltiazem or simvastatin was safe and well tolerated during the interval studied.
机译：在1个开放标签和4个双盲，随机，多剂量研究中，研究了一种新的抗心绞痛化合物雷诺嗪与CYP3A同工酶家族的抑制剂和底物的相互作用。在健康的成年人志愿者中，作者寻求（1）确定有和没有酮康唑，地尔硫卓或辛伐他汀的速释和持续释放雷诺嗪的稳态药代动力学，安全性和耐受性，以及（2）评估雷诺嗪的作用地尔硫卓，辛伐他汀，辛伐他汀代谢产物和HMG-CoA还原酶活性的药代动力学酮康唑增加了雷诺嗪的血浆浓度并降低了CYP3A4介导的雷诺嗪的代谢转化，证实CYP3A4是雷诺嗪的主要代谢途径。地尔硫卓以剂量依赖性方式降低雷诺嗪的口服清除率。辛伐他汀不会影响雷诺嗪的药代动力学，尽管雷诺嗪可使辛伐他汀，辛伐他汀酸，2种辛伐他汀代谢物和HMG-CoA还原酶活性的AUC和C（max）降低<2倍。在研究的间隔期内，将雷诺嗪与地尔硫卓或辛伐他汀联用是安全的，并且耐受性良好。

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