奧貝膽酸是一種治療原發(fā)性膽汁性肝硬化和非酒精性脂肪肝的新型候選藥物,由美國Intercept制藥公司研發(fā),其機制主要是通過激動法尼醇X受體,調(diào)節(jié)相關(guān)基因,影響膽汁酸的合成、分泌、轉(zhuǎn)運和吸收。臨床研究表明,對熊去氧膽酸不能完全耐受的患者,通過服用奧貝膽酸能夠明顯改善堿性磷酸酶和血清膽紅素的水平,提示奧貝膽酸的臨床效果可能優(yōu)于現(xiàn)有藥物熊去氧膽酸。將從奧貝膽酸的藥物概況、相關(guān)背景、合成路線、藥理作用、臨床前及臨床試驗研究以及安全性評價方面進行簡述。

Obeticholic acid is a drug candidate for the treatment of primary biliary cirrhosis and nonalcoholic fatty liver disease, which was developed by Intercept Pharmaceuticals. It mainly regulates related gene and affects the synthesis, secretion, transport, and absorption of bile acid through activating farnesoid X receptor. Clinical studies have shown that obeticholic acid can improve the level of alkaline phosphatase and serum bilirubin to the subjects who cannot inadequate response to ursodeoxycholic acid therapy, so obeticholic acid may be prior to ursodeoxycholic acid. This paper mainly discusses the drug situation, background, route of synthesis, pharmacological action, preclinical, clinical trials research, and safety evaluation.

國家自然科學(xué)基金資助項目(81503130);天津市應(yīng)用基礎(chǔ)與前沿技術(shù)研究計劃(14JCQNJC13000)