布林西多福韋（BCV）是西多福韋（CDV）的長(zhǎng)脂肪側(cè)鏈衍生物，是核苷類(lèi)DNA聚合酶競(jìng)爭(zhēng)性抑制劑。BCV結(jié)構(gòu)中脂質(zhì)部分的引入增加了細(xì)胞攝取和口服生物利用度，使其在保持廣譜抗雙鏈DNA（dsDNA）特性的基礎(chǔ)上有效提高了抗病毒活性。臨床試驗(yàn)表明 BCV對(duì)多種 dsDNA病毒表現(xiàn)出良好的治療效果，并被美國(guó)食品藥品監(jiān)督管理局批準(zhǔn)用于全年齡段天花的治療。BCV不是有機(jī)陰離子轉(zhuǎn)運(yùn)蛋白-1（OAT-1）的底物，腎毒性降低，腹痛、腹瀉等胃腸道癥狀以及血清轉(zhuǎn)氨酶升高是其常見(jiàn)的不良反應(yīng)。就 BCV的作用機(jī)制、藥動(dòng)學(xué)、臨床療效和安全性研究進(jìn)行綜述，為抗 dsDNA病毒藥物研發(fā)及合理用藥提供參考。

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.

R978.7；R969.4

病原微生物生物安全國(guó)家重點(diǎn)實(shí)驗(yàn)室開(kāi)放研究基金資助項(xiàng)目（SKLPBS1818）