Bile acids as drugs: principles, mechanisms of action and formulations.

Bile acid therapy is based on the use of bile acid agonists or bile acid antagonists. Bile acid agonists consist of bile acids or their derivatives. They are used for two purposes. The first is to correct a deficiency in bile acids because of defective biosynthesis or intestinal conservation and thereby to restore bile acid function. This rationale may be termed replacement therapy. The second is to alter the composition of circulating bile acids and thereby to modulate cholesterol metabolism and/or decrease the cytotoxicity of the circulating bile acid pool. This rationale may be termed displacement therapy. Administration of chenodeoxycholic (CDCA) and/or ursodeoxycholic (UDCA) decreases biliary secretion of cholesterol leading to secretion of bile that is unsaturated in cholesterol and gradual dissolution of cholesterol gallstones. Administration of UDCA to patients with chronic cholestatic liver disease lowers the proportion of endogenous cytotoxic dihydroxy bile acids in the circulating bile acids, improves liver tests, and delays liver failure. Bile acid antagonists act to decrease intestinal conservation of bile acids either by sequestering bile acids in the intestinal lumen or by inhibiting bile acid transport by the ileal enterocyte. For therapy, CDCA is administered as the protonated acid and is well absorbed. UDCA is also administered as the protonated acid, but absorption is incomplete. Complete absorption can be obtained using the sodium salt of UDCA in a capsule with a pH-sensitive enteric coating. The taurine conjugate of UDCA is administered as the protonated sulfonic acid, and its absorption requires a carrier mechanism; however, it is likely to undergo rapid deconjugation during enterohepatic cycling, liberating UDCA which can be passively absorbed.(ABSTRACT TRUNCATED AT 250 WORDS)