聚乙二醇化干扰素治疗乙型肝炎的药代动力学和药效学。

StephenW

Expert Opin Drug Metab Toxicol. 2019 Oct 8. doi: 10.1080/17425255.2019.1678584. [Epub ahead of print]
Pharmacokinetics and pharmacodynamics of pegylated interferon for the treatment of hepatitis B.
Yeh ML1,2, Huang JF1,2,3, Dai CY1,2,3, Yu ML1,2,3,4,5, Chuang WL1,2,3.
Author information

1
    Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital , Kaohsiung , Taiwan.
2
    School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University , Kaohsiung , Taiwan.
3
    Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University , Kaohsiung , Taiwan.
4
    Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B) and Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University , Hsin-Chu , Taiwan.
5
    Institute of Biomedical Sciences, National Sun Yat-Sen University , Kaohsiung , Taiwan.

Abstract

Introduction: Interferon (IFN) had both antiviral and immunomodulatory effects, and was one of the approved treatments for hepatitis B virus (HBV). Herein, we reviewed the pharmacokinetics and pharmacodynamics of pegylated IFN-α (PegIFN-α) for the treatment of HBV. Areas covered: The steady-state serum levels of PegIFN-α were reached within 5 to 8 weeks, and the week 48 mean trough concentrations were approximately 2-fold higher than week 1. There was also no difference of the pharmacokinetics in male or female, healthy volunteers or patients with hepatitis B or C infection. PegIFN-α did not affect the metabolism of the cytochrome P450 (CYP) isozymes, except inhibition of CYP1A2. There was also no pharmacokinetic interaction between PegIFN-α and HBV nucleot(s)ide analogues (NUCs). Forty-eight weeks of PegIFN-α achieved 32% of HBeAg seroconversion, 32-43% of HBV DNA suppression, 41-59% of ALT normalization, and 3% of HBsAg seroconversion rate with a post-treatment durable response up to 80% in the initial responders. Expert opinion: On-treatment HBsAg titer guided the treatment of HBV with PegIFN-α. The recommendation of PegIFN-α and NUC combination or switch remained controversial. New immunotherapeutic agents are now in development. Although, PegIFN-α should continue to play a role in the treatment of HBV.
KEYWORDS:

Interferon; Mechanism; Pegylated interferon; Pharmacodynamic; Pharmacokinetic

PMID:
    31593639
DOI:
    10.1080/17425255.2019.1678584

StephenW

专业的奥宾药​​物代谢毒物。 2019年10月8日.doi：10.1080 / 17425255.2019.1678584。 [Epub提前发布]
聚乙二醇化干扰素治疗乙型肝炎的药代动力学和药效学。
是ML1,2，Huang JF1,2,3，Dai CY1,2,3，Yu ML1,2,3,4,5，Chuang WL1,2,3。
作者信息

1个
    台湾高雄市高雄医科大学附属医院内科肝炎中心和肝胆科。
2
    台湾高雄医科大学医学院肝炎研究中心，医学院。
3
    高雄医科大学癌症研究中心和液体活检中心，台湾高雄。
4
    国立交通大学生物科学与技术学院智能药物系统与智能生物设备中心（IDS2B）和生物科学与技术系，台湾新竹。
5
    国立中山大学生物医学研究所，台湾高雄。

抽象

简介：干扰素（IFN）具有抗病毒和免疫调节作用，是批准的乙型肝炎病毒（HBV）治疗药物之一。本文中，我们综述了聚乙二醇化干扰素-α（PegIFN-α）用于治疗HBV的药代动力学和药效学。覆盖区域：PegIFN-α的稳态血清水平在5至8周内达到，并且第48周的平均谷浓度比第1周高出约2倍。男性或女性的药代动力学也没有差异，健康的志愿者或患有乙型或丙型肝炎感染的患者。除抑制CYP1A2外，PegIFN-α不影响细胞色素P450（CYP）同工酶的代谢。 PegIFN-α和HBV核苷酸类似物（NUCs）之间也没有药代动力学相互作用。 48周的PegIFN-α实现了32％的HBeAg血清转化，32-43％的HBV DNA抑制，41-59％的ALT正常化以及3％的HBsAg血清转化率，治疗后的持久应答高达80％在最初的响应者中。专家意见：治疗中HBsAg滴度指导用PegIFN-α治疗HBV。 PegIFN-α和NUC联合使用或改用的建议仍存在争议。现在正在开发新的免疫治疗剂。虽然，PegIFN-α应该继续在HBV的治疗中发挥作用。
关键字：

干扰素机制;聚乙二醇干扰素；药效学；药代动力学

PMID：
    31593639
DOI：
    10.1080 / 17425255.2019.1678584