口服Toll受体7激动剂TQ-A3334在健康个体中的安全性，药代动力

StephenW

Safety, Pharmacokinetics, and Pharmacodynamics of TQ-A3334, an Oral Toll-Like Receptor 7 Agonist, in Healthy Individuals
Hong Zhang  1 , Yue Hu  1 , Min Wu  1 , Jingrui Liu  1 , Xiaojiao Li  1 , Xiaoxue Zhu  1 , Cuiyun Li  1 , Hong Chen  1 , Chengjiao Liu  1 , Junqi Niu  2 , Yanhua Ding  1
Affiliations
Affiliations

    1
    Phase I Clinical Research Center, The First Hospital of Jilin University , Jilin, China.
    2
    Department of Hepatology, The First Hospital of Jilin University , Jilin, China.

    PMID: 33405993 DOI: 10.1080/13543784.2021.1873275

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.

Keywords: HBV; clinical trial; pharmacodynamics; pharmacokinetics; toll-like receptor 7 agonist.

StephenW

口服Toll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
张红1，胡越1，吴敏1，刘静瑞1，李小娇1，朱小雪1，李翠云1，陈宏1，刘成娇1，牛俊琪2，丁艳华1
隶属关系
隶属关系

    1个
    吉林大学第一医院一期临床研究中心，吉林
    2
    吉林大学第一医院肝脏科，吉林

    PMID：33405993 DOI：10.1080 / 13543784.2021.1873275

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，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）。

研究设计和方法：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。

关键字：HBV；临床试验;药效学药代动力学Toll样受体7激动剂。