布林西多福韦治疗双链DNA病毒感染的药理与临床研究进展  

Research progress on pharmacology and clinical assessment of brincidofovir in treatment of dsDNA virus infection

作　　者：曹玢旺 王洪权 王保刚 CAO Binwang;WANG Hongquan;WANG Baogang(State Key Laboratory of Pathogen and Biosecurity,Institute of Microbiology and Epidemiology,Academy of Military Medicine Sciences,Academy of Military Sciences,Beijing 100071,China)

机构地区：[1]军事科学院军事医学研究院微生物流行病研究所,病原微生物生物安全国家重点实验室,北京100071

出　　处：《药物评价研究》2023年第5期1131-1140,共10页Drug Evaluation Research

基　　金：病原微生物生物安全国家重点实验室开放研究基金资助项目(SKLPBS1818)。

摘　　要：布林西多福韦(BCV)是西多福韦(CDV)的长脂肪侧链衍生物,是核苷类DNA聚合酶竞争性抑制剂。BCV结构中脂质部分的引入增加了细胞摄取和口服生物利用度,使其在保持广谱抗双链DNA(dsDNA)特性的基础上有效提高了抗病毒活性。临床试验表明BCV对多种dsDNA病毒表现出良好的治疗效果,并被美国食品药品监督管理局批准用于全年龄段天花的治疗。BCV不是有机阴离子转运蛋白-1(OAT-1)的底物,肾毒性降低,腹痛、腹泻等胃肠道症状以及血清转氨酶升高是其常见的不良反应。就BCV的作用机制、药动学、临床疗效和安全性研究进行综述,为抗dsDNA病毒药物研发及合理用药提供参考。Brincidofovir(BCV)is a lipid conjugate of cidofovir(CDV),a competitive inhibitor of viral DNA polymerase.The lipid conjugation results in oral bioavailability,higher intracellular concentrations of active drug,maintained broad-spectrum,and increased antiviral potency against double-stranded DNA(dsDNA)viruses.Clinical trials have shown that BCV can be effective against multiple dsDNA viruses,and it has been approved by the U.S.Food and Drug Administration for the treatment of smallpox in all age groups.Unlike CDV,BCV is not a substrate for the organic anion transporter-1(OAT-1)which explains the lack of nephrotoxicity observed.Gastrointestinal symptoms such as abdominal pain and diarrhea and elevated serum transaminases are common adverse effects of BCV.This paper provides an overview of the mechanism of action,pharmacokinetic properties,clinical effects,and safety of BCV,which can provide reference for the development of anti-dsDNA virus drugs and rational use of BCV.

关 键 词：布林西多福韦 西多福韦 双链DNA病毒 有机阴离子转运蛋白-1 合理用药 

分 类 号：R978.7[医药卫生—药品] R969.4[医药卫生—药学]