单剂药物动力学的boceprevir受试者肝或肾功能受损。

文章的细节

引用

复制到剪贴板

Treitel M,马布里T,普雷斯顿RA, Triantafyllou我,费利W O ' mara E, Kasserra C,古普塔年代,休斯EA

单剂药物动力学的boceprevir受试者肝或肾功能受损。

Pharmacokinet。2012年9月1日,51 (9):619 - 28。doi: 10.2165 / 11633440-000000000-00000。

PubMed ID

22799589 (在PubMed

]

文摘

背景和目的:Boceprevir是一种新型抑制剂的丙型肝炎病毒NS3蛋白酶和最近被批准用于治疗慢性丙型肝炎患者的感染。本研究的目的是评价肝或肾功能受损的影响boceprevir药物动力学和安全/耐受性。方法:我们进行了两次非盲、单剂,与这些相应平行的组织比较boceprevir安全性和药物动力学的研究对不同程度的肝损伤患者与健康对照组相比,在一项研究中,终末期肾病(ESRD)患者与健康对照组血液透析。肝损伤患者轻微(n = 6),中等(n = 6)严重(n = 6)和健康对照组(n = 6))收到了一剂boceprevir(400毫克)1天,和全血收集在指定时间点多达72小时postdose测量血浆药物浓度。ESRD患者和健康者收到的boceprevir 800毫克口服单剂量天1和4,药代动力学分析的样品收集在指定时间点postdose 48小时在这两天。此外,4小时后加药4天,ESRD患者接受血液透析与动脉和静脉血样采集postdose 8个小时。结果:在肝损伤的研究中,有一个趋势增加意味着最大(峰)血浆浓度(C (max))和血浆浓度时间曲线下面积(AUC) boceprevir越来越严重的肝损伤。点估计为几何平均比C (max)范围从100%轻度肝损害患者161%有严重肝损伤患者,AUC的几何平均比率从91%轻度肝损害患者有严重肝损伤患者的149%,相对于健康受试者。意味着消除半衰期(t(1/2;))和平均时间C (max) (t (max))值的boceprevir相似在健康受试者和肝损伤患者。在肾损伤的研究中,意味着boceprevir C (max)和AUC值可比ESRD患者在健康受试者,与点估计几何平均比率为81%和90%,分别与健康受试者相比。 Mean t(1/2;), median t(max) and mean apparent oral total clearance (CL/F) values were similar in healthy subjects and patients with ESRD. Boceprevir exposure was also similar in patients with ESRD on day 1 (no dialysis) and day 4 (dialysis beginning 4 hours postdose), with point estimates for the geometric mean ratio of C(max) and AUC to the last measurable sampling time (AUC(last)) on day 1 compared with day 4 of 88% and 98%, respectively. Treatment-emergent adverse events were reported in one patient with severe hepatic impairment (mild vomiting) and two patients with ESRD (moderate ventricular extrasystoles, flatulence and catheter thrombosis). CONCLUSION: In the present studies, the pharmacokinetic properties of boceprevir were not altered to a clinically meaningful extent in patients with impaired liver or renal function. These data indicate that boceprevir dose adjustment is not warranted in patients with impaired hepatic function or ESRD, including those receiving dialysis. Boceprevir is not removed by haemodialysis.

DrugBank数据引用了这篇文章

药物

Boceprevir