Clinical evaluation of efficacy, tolerability and pharmacokinetics of yimitasvir phosphate in patients infected with hepatitis C virus
Clinical evaluation of efficacy, tolerability and pharmacokinetics of yimitasvir phosphate in patients infected with hepatitis C virus
复制标题
磷酸依米他韦对丙型肝炎病毒感染患者的疗效、耐受性和药代动力学的临床评价。
DOI：
10.1111/jphp.12916
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发表时间：
2018-07-01
影响因子：
3.3
通讯作者：
Niu, Junqi
中科院分区：
文献类型：
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作者：
Zhang, Hong;Zhu, Xiaoxue;Niu, Junqi
Yimitasvir磷酸盐，抑制剂的非结构蛋白5A（NS 5A）复制复合物的丙型肝炎病毒（HCV），在双盲，安慰剂对照，平行，多剂量study.MethodsTwenty-four慢性HCV基因型1感染的患者随机接受为期7天的疗程的Yimitasvir磷酸盐在每日剂量为30，100或200毫克或安慰剂。抗病毒疗效，耐药性，药代动力学（PK），安全性和耐受性进行了评估。然而，大多数患者在开始伊米他韦治疗后的第3天或之前经历了病毒反弹。PK曲线显示给药后4-12 h的中位血浆峰浓度和平均终末半衰期为14.47-17.09 h，这是每日给药的基础。每日给药5天后达到药物稳态。累积率较低（1.29-1.73）。有没有生命体征和实验室检查结果之间的所有participant.ConclusionsThis研究表明，磷酸伊米他韦耐受性良好，和PK曲线支持每日给药方案的显着改变。1周（7天）疗程导致HCV GT-1感染队列中HCV RNA水平快速显著降低。
ObjectiveYimitasvir phosphate, an inhibitor of nonstructural protein 5A (NS5A) replication complex of hepatitis C virus (HCV), was evaluated in a double-blind, placebo-controlled, parallel, multiple-dose study.MethodsTwenty-four patients with chronic HCV genotype 1 infection were randomized to receive a 7-day course of yimitasvir phosphate at daily doses of 30, 100 or 200 mg or placebo. Antiviral efficacy, resistance profile, pharmacokinetics (PK), safety and tolerability were assessed.Key findingsThe maximal reduction in HCV RNA from baseline was 5.17 log(10) IU/ml. However, most patients experienced viral rebound on or before day 3 after yimitasvir treatment was initiated. The PK profile revealed median peak plasma concentrations at 4-12 h postdose and a mean terminal half-life of 14.47-17.09 h, the basis for daily dosing. Steady drug state was achieved following 5 days of daily dosing. The accumulation rate was low (1.29-1.73). There were no significant alterations in vital signs and laboratory findings among all participants.ConclusionsThis study shows that yimitasvir phosphate was well tolerated, and the PK profile supported daily dosing regimens. A 1-week (7-day) treatment course led to a quick and significant reduction in HCV RNA level in this cohort with HCV GT-1 infection.