所需浓度指数量化抗丙型肝炎病毒感染的有效药物组合。

Pub Date : 2021-01-09 DOI:10.1186/s12976-020-00135-6
Yusuke Kakizoe, Yoshiki Koizumi, Yukino Ikoma, Hirofumi Ohashi, Takaji Wakita, Shingo Iwami, Koichi Watashi
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引用次数: 1

摘要

成功的临床药物开发需要基于临床前数据合理设计联合治疗方案。抗丙型肝炎病毒(HCV)药物在抗病毒作用上表现出显著的多样性。剂量反应评估可用于确定综合治疗期间不同抗病毒效果的参数。在目前的研究中,采用实验和数学相结合的方法来比较和评分不同的抗hcv治疗组合。生成了一个“所需浓度指数”,并用于对可能的双药和三联药联合治疗1b和2a型HCV的抗病毒特性进行排序。排名因目标HCV基因型而异。有趣的是,多药(双药和三联药)治疗不仅增强了抗病毒活性,而且降低了基因型特异性疗效,这表明多药治疗的另一个优势。目前的研究提供了一种定量方法来分析针对病毒基因型的药物组合,从而更好地为临床药物开发提供信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Required concentration index quantifies effective drug combinations against hepatitis C virus infection.

Required concentration index quantifies effective drug combinations against hepatitis C virus infection.

Required concentration index quantifies effective drug combinations against hepatitis C virus infection.

Required concentration index quantifies effective drug combinations against hepatitis C virus infection.

Successful clinical drug development requires rational design of combination treatments based on preclinical data. Anti-hepatitis C virus (HCV) drugs exhibit significant diversity in antiviral effect. Dose-response assessments can be used to determine parameters profiling the diverse antiviral effect during combination treatment. In the current study, a combined experimental and mathematical approaches were used to compare and score different combinations of anti-HCV treatments. A "required concentration index" was generated and used to rank the antiviral profile of possible double- and triple-drug combinations against HCV genotype 1b and 2a. Rankings varied based on target HCV genotype. Interestingly, multidrug (double and triple) treatment not only augmented antiviral activity, but also reduced genotype-specific efficacy, suggesting another advantage of multidrug treatment. The current study provides a quantitative method for profiling drug combinations against viral genotypes, to better inform clinical drug development.

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