贝西福韦治疗HBV感染的药代动力学评价。

StephenW

Expert Opin Drug Metab Toxicol. 2017 Dec 13. doi: 10.1080/17425255.2018.1417983. [Epub ahead of print]
Pharmacokinetic evaluation of besifovir for the treatment of HBV infection.Mak LY1, Seto WK1,2, Lai CL1,2, Yuen MF1,2.
Author information
1a Department of Medicine , The University of Hong Kong, Queen Mary Hospital , Hong Kong.2b State Key Laboratory for Liver Research , The University of Hong Kong , Hong Kong.

AbstractBesifovir (LB80380) is a relatively new oral acyclic nucleotide phosphonate. We reviewed the pharmacokinetic characteristics of LB80380 and discussed its role in the treatment of chronic hepatitis B infection. Areas covered: LB80380 is a prodrug of LB80331 and LB8031. It is rapidly absorbed when taken orally. Escalating doses of besifovir produce linear increase of the plasma concentration. Doses above 60mg are effective for inhibiting HBV in human. Using 60mg as an example, the maximal concentration of LB80331 in plasma is 397 ng/mL. The time required to reach maximal concentration in plasma and elimination half-life are 2.0 and 3.0 hours, respectively. Besifovir and its metabolites are mainly excreted via the kidneys. Its antiviral efficacy is non-inferior to ETV 0.5mg daily. It is generally safe in terms of renal and bone toxicity. The most common adverse event is carnitine depletion which affects almost all patients on besifovir requiring carnitine supplementation. Expert opinion: Besifovir demonstrated predictable pharmacokinetic characteristics in human subjects. Few clinical studies on besifovir have been conducted. More data are expected particularly for special populations. The adverse events upon long term exposure should be monitored. Large scale head-to-head trials comparing besifovir with existing NA, especially tenofovir alafenamide, should be conducted.


KEYWORDS: adverse effects; besifovir; carnitine; efficacy; hepatitis B virus; humans; nucleotide analogue; pharmacokinetics; renal toxicity

PMID:29237296DOI:10.1080/17425255.2018.1417983

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StephenW

药物代谢毒性药物专家意见。 2017 Dec 13。doi：10.1080 / 17425255.2018.1417983。 [电子版提前打印]
贝西福韦治疗HBV感染的药代动力学评价。
Mak LY1，Seto WK1,2，Lai CL1,2，Yuen MF1,2。
作者信息

1
香港玛丽医院香港大学医学系。
2
b香港大学肝脏研究国家重点实验室。

抽象

我们回顾了LB80380的药代动力学特征，并讨论了它在治疗慢性乙型肝炎感染中的作用。覆盖范围：LB80380是LB80331和LB8031的前体药物。口服时被迅速吸收。升高剂量的besifovir会使血浆浓度线性增加。 60mg以上的剂量对人体内的HBV有抑制作用。以60mg为例，血浆中LB80331的最大浓度为397ng / mL。达到其抗病毒疗效所需的时间并不劣于每天0.5毫克的ETV。肾和骨的毒性通常是安全的。最常见的不良事件是左旋肉碱耗竭，几乎所有患者都需要补充左旋肉碱。专家意见：贝西福韦在人类受试者中表现出可预测的药代动力学特征。很少有关于besifovir的临床研究。预计更多的数据特别针对特殊人群。应该监测长期暴露的不良事件。大规模的头对头试验动物应该是beifovir与现有的NA，尤其是替诺福韦alafenamide，应该进行。
关键词：

不利影响; besifovir;左旋肉碱;功效;乙肝病毒;人类;核苷酸类似物;药代动力学;肾毒性

结论：
29237296
DOI：
10.1080 / 17425255.2018.1417983

Hepbest

回复 StephenW 的帖子

besifovir 也是TFV族的药物，效果应该不优于替诺？
还是和TAF类似？

StephenW

回复 Hepbest 的帖子

根据临床研究, besifovir和TDF,一样有效, 但较少肾和骨密度副作用.
但besifovir有肉碱耗尽(carnitine depletion)副作用.
像TAF一样, besifovir需要更多的治疗经验.

相信科学家

回复 StephenW 的帖子

搞来搞去就是核苷类与核苷酸类，这两类中恩替卡韦与TAF已经到达巅峰了。现在需要的是要么是更进一步的药物，比如能让表面抗原阴转的药物，要么起码也是与当前药物无交叉耐药的抗病毒类药物，否则没有市场前景。

StephenW

回复 相信科学家 的帖子

besifovir研究始于10年前. 现在环境完全不同了.