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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Assessment of the potential pharmacokinetic and pharmacodynamic interactions between erythromycin and argatroban.
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Assessment of the potential pharmacokinetic and pharmacodynamic interactions between erythromycin and argatroban.

机译：评估红霉素和阿加曲班之间潜在的药代动力学和药效动力学相互作用。

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摘要

Argatroban, a direct thrombin inhibitor, is metabolized in vitro by CYP3A4/5 and therefore may be susceptible to clinically relevant CYP3A drug interactions. The effect of erythromycin, a potent CYP3A4/5 inhibitor, on the pharmacokinetics and pharmacodynamics of argatroban was evaluated in 14 healthy male volunteers in an open-label, crossover study with a 5-day washout between regimens. Argatroban 1 microgram/kg/min was infused alone for 5 hours (regimen A) and again on day 6 of a 7-day oral regimen of 500 mg erythromycin four times daily (regimen B). Serial blood samples for the determination of activated partial thromboplastin time (aPTT) and argatroban concentrations were collected for up to 48 hours following infusion. Mean values for argatroban area under the concentration-time curves (AUC0-inf), maximum concentration (Cmax), and half-life (t1/2) were similar between regimens. Mean aPTT values were not affected significantly by the concomitant administration of argatroban and erythromycin compared to argatroban alone. No serious adverse events or bleeding episodes occurred during the study. These results suggest that oxidative metabolism by CYP3A4/5 is unlikely to be an important in vivo elimination pathway for argatroban. Therefore, coadministration of CYP3A4/5 inhibitors should not require a modification in the dosage of argatroban.
机译：Argatroban是一种直接的凝血酶抑制剂，在体外被CYP3A4 / 5代谢，因此可能与临床相关的CYP3A药物相互作用敏感。在一项开放标签，交叉研究中，在方案之间进行了5天的洗脱研究，评估了14名健康男性志愿者中红霉素（一种有效的CYP3A4 / 5抑制剂）对argatroban的药代动力学和药效学的影响。单独注入1毫克/千克/分钟的Argatroban 5小时（方案A），然后在7天口服500 mg红霉素的7天口服方案的第6天再次注入（方案B）。输注后长达48小时，收集用于确定活化的部分凝血活酶时间（aPTT）和阿加曲班浓度的系列血样。两种方法在浓度-时间曲线（AUC0-inf），最大浓度（Cmax）和半衰期（t1 / 2）下的阿加曲班面积均值相似。与单独使用阿加曲班相比，同时给予阿加曲班和红霉素对平均aPTT值影响不明显。在研究期间没有发生严重的不良事件或出血事件。这些结果表明CYP3A4 / 5的氧化代谢不太可能是argatroban的重要体内消除途径。因此，CYP3A4 / 5抑制剂的共同给药不需要改变argatroban的剂量。

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