口服Toll样受体7激动剂TQ-A3334在健康个体中的安全性，药代动

StephenW

Safety, pharmacokinetics and pharmacodynamics of TQ-A3334, an oral toll-like receptor 7 agonist in healthy individuals
Yue Hu , Hong Zhang , Min Wu , Jingrui Liu , Xiaojiao Li , Xiaoxue Zhu , show all
Received 28 Oct 2020, Accepted 05 Jan 2021, Accepted author version posted online: 06 Jan 2021, Published online: 13 Jan 2021

    Download citation https://doi.org/10.1080/13543784.2021.1873275 CrossMark Logo CrossMark

In this article

    ABSTRACT
    1. Introduction
    2. Materials and Methods
    3. Results
    4. Discussion
    5. Conclusion
    Supplemental material
    Additional information
    References

ABSTRACT
Background & Aims

TQ-A3334, a selective, oral toll-like receptor (TLR)-7 agonist, is being developed to treat chronic hepatitis B (CHB). This study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of TQ-A3334 in healthy participants.
Research design and methods

The effects of a single-ascending dose of TQ-A3334 (0.2–1.8 mg) combined with food (1.2 mg) were evaluated in 48 healthy participants.
Results

No serious adverse events or discontinuations occurred in the study. The most common adverse reactions were lymphocyte count decreased and headache, which were generally consistent with IFN-α exposure and the mechanism of action of a TLR7 agonist. TQ-A3334 was rapidly absorbed, with a time to maximum plasma concentration of 0.42–0.5 h. Systemic exposure (Cmax and AUC) to TQ-A3334 increased with a slight saturation proportion to dose. Food reduced the exposure of TQ-A3334. The concentrations of MCP-1, ISG-15, MX-1, and OAS-1 were observed to be slightly dose-dependent, ranging from 1.0 to 1.8 mg TQ-A3334.
Conclusions

Oral doses of 0.2–1.8 mg appeared to be safe and tolerated. PD activity was seen at doses ranging from 1.0 to 1.8 mg, indicating its possible future use to treat CHB.
Trial Registration

The trial is registered at the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html # CTR20182248).

KEYWORDS: Clinical trialpharmacodynamicspharmacokineticstoll-like receptor 7 agonisthbv

StephenW

口服Toll样受体7激动剂TQ-A3334在健康个体中的安全性，药代动力学和药效学
胡跃，张宏，吴敏，刘静瑞，李晓娇，朱晓雪，全部显示
2020年10月28日收到，2021年1月5日接受，在线接受作者版本：2021年1月6日，在线发表：2021年1月13日

    下载引文https://doi.org/10.1080/13543784.2021.1873275 CrossMark徽标CrossMark

在这篇文章中

    抽象
    1.简介
    2。材料和方法
    3.结果
    4。讨论
    5.结论
    补充材料
    附加信息
    参考文献

抽象
背景与目标

TQ-A3334是一种选择性的口服收费类似受体（TLR）-7激动剂，目前正在开发中，用于治疗慢性乙型肝炎（CHB）。这项研究评估了TQ-A3334在健康受试者中的安全性，药代动力学（PK）和药效学（PD）。
研究设计与方法

在48位健康参与者中评估了单次递增剂量的TQ-A3334（0.2-1.8 mg）与食物（1.2 mg）的联合作用。
结果

在研究中没有发生严重的不良事件或停药。最常见的不良反应是淋巴细胞数量减少和头痛，这通常与IFN-α暴露以及TLR7激动剂的作用机制一致。 TQ-A3334被快速吸收，达到最大血浆浓度的时间为0.42-0.5 h。 TQ-A3334的全身暴露（Cmax和AUC）以与剂量略有饱和的比例增加。食物减少了TQ-A3334的暴露。观察到MCP-1，ISG-15，MX-1和OAS-1的浓度略有剂量依赖性，范围从1.0到1.8 mg TQ-A3334。
结论

口服剂量为0.2–1.8 mg似乎是安全且可以耐受的。在1.0至1.8 mg的剂量范围内可观察到PD活性，表明其将来可能用于治疗CHB。
试用注册

该试验已在中国临床试验网站（http://www.chinadrugtrials.org.cn/index.html＃CTR20182248）上注册。

关键词：临床试验药效学药代动力学Toll样受体7激动剂HBV

StephenW

https://www.tandfonline.com/doi/ ... 275?needAccess=true