前药策略提高核苷类抗病毒抑制剂的疗效。
Prodrug strategies for improved efficacy of nucleoside antiviral inhibitors.
机构信息
aLaboratory of Biochemical Pharmacology, Department of Pediatrics, Center for AIDS Research, Emory University School of Medicine, Atlanta, Georgia, USA bVeterans Affairs Medical Center, Decatur, Georgia, USA.
出版信息
Curr Opin HIV AIDS. 2013 Nov;8(6):556-64. doi: 10.1097/COH.0000000000000007.
PURPOSE OF REVIEW
This review focuses on the chemical and pharmacological rationale behind the development of nucleoside antiviral prodrugs (NAPs).
RECENT FINDINGS
Highly efficacious NAPs have been developed that extend and improve the quality of lives of individuals infected with HIV and hepatitis B virus (HBV), herpes viruses, and adenovirus infection in immunocompromised individuals. A very high rate of hepatitis C virus (HCV) cure is now possible using NAPs combined with other direct acting antiviral agents (DAAs).
SUMMARY
Prodrug strategies can address the issues of poor oral bioavailability and delivery of active metabolites to the targeted cells. Additionally, NAPs demonstrate potential for improving deficiencies in oral absorption, metabolism, tissue distribution, cellular accumulation, phosphorylation, and overall potency, in addition to diminishing potential for in-vivo selection of resistant viruses. NAPs continue to be the backbone for the treatment of HIV and HBV, herpesviruses, and adenovirus infections because their active forms are potent, have long intracellular half-lives and are relatively safe with high barrier to resistance.
目的综述
本文重点介绍了核苷抗病毒前药（NAPs）开发背后的化学和药理学原理。
最近的发现
已经开发出高效的 NAPs，可延长和改善感染 HIV 和乙型肝炎病毒（HBV）、疱疹病毒以及免疫功能低下个体中腺病毒感染的个体的生活质量。现在，使用 NAPs 联合其他直接作用抗病毒药物（DAAs），丙型肝炎病毒（HCV）的治愈率非常高。
摘要
前药策略可以解决生物利用度差和将活性代谢物递送到靶细胞的问题。此外，NAPs 具有改善口服吸收、代谢、组织分布、细胞积累、磷酸化和整体效力的潜力，同时降低体内选择耐药病毒的潜力。NAPs 仍然是治疗 HIV 和 HBV、疱疹病毒和腺病毒感染的基础，因为它们的有效形式具有强大的作用，具有较长的细胞内半衰期，并且具有较高的耐药性屏障，相对安全。
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