综述文章：当前和研究性乙型肝炎病毒疗法的临床药理学。

StephenW

Aliment Pharmacol Ther. 2019 Dec 16. doi: 10.1111/apt.15581. [Epub ahead of print]
Review article: clinical pharmacology of current and investigational hepatitis B virus therapies.
Smolders EJ1,2,3, Burger DM3, Feld JJ4, Kiser JJ1.
Author information

1
    Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus (AMC), Aurora, CO, USA.
2
    Department of Pharmacy, Isala Hospital, Zwolle, The Netherlands.
3
    Department of Pharmacy, Radboud Institute of Health Sciences (RIHS), Radboud university medical center, Nijmegen, The Netherlands.
4
    Toronto Centre for Liver Disease, University of Toronto University Health Network, Toronto, ON, Canada.

Abstract
BACKGROUND:

Treatment of hepatitis B virus (HBV) infection with current therapy suppresses HBV DNA, but loss of hepatitis B surface antigen (HBsAg; functional cure), is rare. Multiple compounds are under investigation.
AIMS:

To describe the pharmacology, including drug interactions, efficacy, safety and mechanisms of action of investigational compounds for HBV infection.
METHODS:

Descriptive review using PubMed and Google to identify literature/conference papers on investigational compounds (≥Phase 2) with data on efficacy and safety in HBV-infected patients.
RESULTS:

Bulevirtide, JNJ-56136379, ABI-H0731, REP-2139, and inarigivir decrease HBV DNA/RNA, with greater potency than current nucleos(t)ide analogues. REP-2139 (25%-75% of patients, 20-48 weeks treatment) and inarigivir (26% of patients, 12-24 weeks treatment) induce HBsAg loss. ARO-HBV reduced (>1.5 log10 UI/mL) HBsAg in 85% of patients (12 weeks treatment). There are some safety concerns with investigational agents (e.g., increased bile acids with bulevirtide, and liver enzyme flares with REP-2139) which will require a risk benefit assessment compared with current therapies. Single and multidose pharmacokinetic data are available for bulevirtide, JNJ-56136379, ABI-H0731; no such data are available for REP-2139, ARO-HBV, inarigivir. Initial drug interaction assessments have been performed with bulevirtide and inarigivir (only in vitro).
CONCLUSION:

There are promising investigational therapies for HBV infection. Increasing the potential for HBsAg loss may result in more patients achieving functional cure. However, many knowledge gaps remain such as pharmacokinetics in those with HBV, cirrhosis and renal impairment but also the interaction potential between investigational therapies, risk-benefit profiles, and potential for drug interactions with medications used to treat comorbidities associated with aging.

© 2019 John Wiley & Sons Ltd.

PMID:
    31840863
DOI:
    10.1111/apt.15581

StephenW

食品药理学。 2019年12月16日.doi：10.1111 / apt.15581。 [Epub提前发布]
综述文章：当前和研究性乙型肝炎病毒疗法的临床药理学。
Smolders EJ1,2,3，Burger DM3，Feld JJ4，Kiser JJ1。
作者信息

1个
    美国科罗拉多州奥罗拉市科罗拉多大学安舒兹医学院（AMC）斯卡格斯药学院和药学院的药物科学系。
2
    荷兰兹沃勒Isala医院药房。
3
    荷兰奈梅亨的拉德布德大学医学中心，拉德布德健康科学研究所（RIHS）药房。
4
    加拿大安大略省多伦多大学多伦多大学卫生网络多伦多肝病中心。

抽象
背景：

用当前疗法治疗乙型肝炎病毒（HBV）感染可抑制HBV DNA，但很少丢失乙型肝炎表面抗原（HBsAg；功能性治愈）。多种化合物正在研究中。
目的：

描述药理学，包括药物相互作用，功效，安全性和研究化合物对HBV感染的作用机理。
方法：

使用PubMed和Google进行描述性审查，以鉴定有关研究化合物（≥2期）的文献/会议论文，并提供有关HBV感染患者的功效和安全性数据。
结果：

Bulevirtide，JNJ-56136379，ABI-H0731，REP-2139和inarigivir降低HBV DNA / RNA的效力比目前的核苷酸类似物更高。 REP-2139（25％-75％的患者，治疗20-48周）和inarigivir（26％的患者，治疗12-24周）引起HBsAg丢失。 ARO-HBV在85％的患者（治疗12周）中降低了（> 1.5 log10 UI / mL）HBsAg。研究药物存在一些安全隐患（例如，与breevirtide一起增加胆汁酸，与REP-2139一起引起肝酶爆发），与目前的疗法相比需要风险评估。单药和多药的药代动力学数据可用于bulevirtide，JNJ-56136379，ABI-H0731;没有REP-2139，ARO-HBV和inarigivir的此类数据。最初的药物相互作用评估是使用bulevirtide和inarigivir（仅在体外）进行的。
结论：

HBV感染有很好的研究方法。增加HBsAg丢失的可能性可能导致更多的患者实现功能性治愈。但是，仍然存在许多知识鸿沟，例如HBV，肝硬化和肾功能不全患者的药代动力学，以及研究疗法之间的相互作用潜力，风险-收益状况以及与用于治疗与衰老相关的合并症的药物之间的相互作用。

©2019 John Wiley＆Sons Ltd.

PMID：
    31840863
DOI：
    10.1111 / apt.15581

StephenW

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/apt.15581