Effect of cholestyramine on bile acid pattern and synthesis during administration of ursodeoxycholic acid in man

Background Cholestyramine is the first-line treatment for cholestasis-induc ed pruritus and is prescribed along with ursodeoxycholic acid (UDCA) in pat ients with cholestatic liver diseases. Impairment of the intestinal absorpt ion of endogenous hydrophobic bile acids by cholestyramine is well known. I t is unclear, however, whether cholestyramine also impairs the absorption o f the hydrophilic bile acid, UDCA, in man. Aims To study serum levels of UDCA and endogenous bile acids as well as end ogenous bile acid synthesis during simultaneous or separate administration of UDCA and cholestyramine in vivo; and absorption of UDCA both in the pres ence and absence of its hydrophobic epimer, chenodeoxycholic acid (CDCA), b y cholestyramine in vitro. Patients and methods Five healthy subjects received UDCA (12.5 +/- 0.5 mg k g(-1) daily) as a single dose for periods of 14 days with or without choles tyramine (4 g daily). Fasting serum levels of bile acids and of 7 alpha-hyd roxy-4-cholesten-3-one (alpha-HC), a measure of endogenous bile acid synthe sis, were determined by gas chromatography and high pressure liquid chromat ography, respectively. In vitro, bile acid solutions were incubated for 24 h in the presence or absence of cholestyramine, and bile acid concentration s were determined in the supernatant. Results Simultaneous administration of UDCA and cholestyramine in man led t o a decrease of fasting serum levels of UDCA by 60% when compared to UDCA s erum levels during administration of UDCA alone. In contrast, serum levels of endogenous bile acids were not affected and alpha-HC serum levels were f ound increased 2.7-fold indicating stimulation of endogenous bile acid synt hesis by cholestyramine. Administration of cholestyramine and UDCA at an in terval of 5 h tended to diminish the effect of cholestyramine on UDCA serum levels. In vitro, conjugated and unconjugated UDCA were effectively bound by cholestyramine both in the presence and absence of hydrophobic bile acid s. Conclusions The results strongly support the recommendation to administer U DCA and cholestyramine at different times of day.