Treatment Effect of Rifampicin on Cholestasis

Abstract

Rifampicin, a semisynthetic antibiotic, has been discovered serendipitously to have beneficial effect on cholestasis. The mechanism, as recently demonstrated, is its induction of pregnane X receptor to regulate the genes involved in bile acids biosynthesis, detoxification and transportation. Thus, toxic bile acids like lithocholic acid are hydrolysed by increased CYP3A4 into a less toxic form. Activation of efflux pumps also facilitates excretion of bile acids from hepatic cells. Furthermore, rifampicin inhibits CYP7A1, a rate-limiting enzyme in the conversion of cholesterol into bile acids, and so reducing bile acids synthesis. However, rifampicin also causes hepatotoxicity in some cases. This limits its use in the treatment of cholestasis. The prospective approaches to overcome the problems could be to find modification of rifampicin chemical structure or find other inducers.