伏立康唑和苯妥英联用:药代动力学相互作用、安全性和耐受性。
文章的细节
-
引用
复制到剪贴板 -
Purkins L, Wood N, Ghahramani P, Love ER, Eve MD, Fielding A
伏立康唑和苯妥英联用:药代动力学相互作用、安全性和耐受性。
临床药物学杂志。2003年12月;56增刊1:37-44。doi: 10.1046 / j.1365-2125.2003.01997.x。
- PubMed ID
-
14616412 (PubMed视图］
- 摘要
-
目的:伏立康唑是一种新型三唑类抗真菌药物，由细胞色素P450同工酶CYP2C9、CYP2C19代谢，少量由CYP3A4代谢。苯妥英是CYP3A4活性的诱导剂，也是CYP2C9和CYP2C19的底物和诱导剂。本研究探讨了伏立康唑与苯妥英联用时的药代动力学相互作用。方法:在健康男性志愿者中进行了两项安慰剂对照的平行组研究。研究A是一项开放标签研究，研究了苯妥英(300 mg，每日1次)对伏立康唑(200 mg和400 mg，每日2次)稳态药代动力学的影响。研究B是一项双盲随机研究，旨在研究伏立康唑(400 mg，每日2次)对苯妥英(300 mg，每日1次)稳态药代动力学的影响。在第7、21和28天(研究A)以及第7和17天(研究B)比较Cmax和AUCtau。记录所有不良事件。结果:研究A: 21名受试者可评估(10名伏立康唑+苯妥英，11名伏立康唑+安慰剂)。对于接受伏立康唑(200mg，每日2次)+苯妥英的受试者，伏立康唑Cmax和AUCtau的第21天/第7天比值分别为60.7%(90%置信区间(CI) 50.1, 73.6)和35.9% (90% CI 29.7, 43.3)。经伏立康唑+安慰剂调整后，均数之比分别为50.7% (90% CI 38.8, 66.1)和30.6% (90% CI 23.5, 39.7)。 When the dose of voriconazole was increased to 400 mg twice daily, the day 28/day 7 ratios for voriconazole Cmax and AUCtau were 134% (90% CI 89.2, 200) and 139% (90% CI 97.3, 199), respectively. Study B: 15 subjects were evaluable for pharmacokinetic assessments (six phenytoin + voriconazole, nine phenytoin + placebo). The ratios between the means for phenytoin + voriconazole/phenytoin + placebo on day 17 vs. day 7 were: phenytoin Cmax 167% (90% CI 144, 193) and phenytoin AUCtau 181% (90% CI 156, 210). All treatments were well tolerated: most adverse events were mild/moderate and transient. CONCLUSIONS: Repeat dose administration of phenytoin decreased the mean steady-state Cmax and AUCtau of voriconazole by approximately 50% and 70%, respectively. Increasing the dose of voriconazole from 200 mg to 400 mg b.d. compensated for this effect. Repeat dose administration of 400 mg b.d. voriconazole increased the mean steady-state Cmax and AUCtau of phenytoin by approximately 70% and 80%, respectively. It is therefore recommended that plasma phenytoin concentrations are monitored and the dose adjusted as appropriate when phenytoin is coadministered with voriconazole.
引用本文的药物库数据
- 药物酶
-
药物 酶 种类 生物 药理作用 行动 苯妥英 细胞色素P450 3A4 蛋白质 人类 没有底物诱导物细节 - 药物的相互作用Learn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
-
药物 交互 整合药物之间
软件中的交互伏立康唑 Fosphenytoin 伏立康唑与磷苯妥英联用可降低血药浓度。 伏立康唑 苯妥英 伏立康唑与苯妥英联用可降低血药浓度。
