Chenodeoxycholic acid¹ (chenic acid; CDCA) is 1 of the 3 major biliary bile acids in man. When administered in pharmacological doses it causes a decrease in cholesterol saturation of bile, which in turn may lead to gradual dissolution of cholesterol gallstones. The stone dissolution rate during CDCA therapy has varied considerably from about one- third of patients overall to 80 to 90 % in a highly selected group of patients. Radiolucent gallstones in a functioning gallbladder are absolute requirements. CDCA is well tolerated; diarrhoea (sometimes requiring dosage reduction) is the only frequent side effect. Although hepatotoxicity has occurred in certain animal species, and slight hypertransaminasaemia has occurred in some patients, definite liver damage has not been observed in man. CDCA is considered contraindicated in pregnancy, and in those patients with the complications from gallstones which require immediate surgery. Care should be taken in patients with liver disease.

The only other proven agent for dissolving gallstones is the 7β-epimer of CDCA, ursodeoxycholic acid (UDCA). Preliminary results show that UDCA is as effective as CDCA, but at one- half to two- thirds the dose, without causing diarrhoea. Further studies need to be done with both CDCA and UDCA to improve criteria for selection of patients most likely to respond, and to establish optimum schedules for dosage and duration of treatment.

Chenodeoxycholic acid is 1 of the 2 primary bile acids synthesised in human liver. Conjugated with either taurine or glycine, it normally makes up approximately one-third of total biliary bile acids. Normal synthesis of CDCA is autoregulated by the relative composition of bile and the bile acid flux through the hepatocyte.

When given orally in pharmacological doses of 10 to 15mg/kg/day, CDCA represents 70 to 95% of the biliary bile acids. At these levels cholesterol secretion into bile is reduced, both in absolute terms and relative to bile acids and phospholipids, the 2 agents that hold cholesterol in micellar solution in bile. Reduced cholesterol saturation allows for the gradual solubilisation of cholesterol from gallstones, leading to their eventual dissolution. In healthy subjects, and in gallstone patients, the saturation of bile with cholesterol varies throughout the day, often being supersaturated when fasting. CDCA therapy renders bile unsaturated in the fasting state, in which case it is likely to be unsaturated for at least 75% of the day.

The mechanism of action of pharmacological doses of CDCA is still unclear. While uncoupling the normal relationship between cholesterol, phospholipid and bile acid secretion, CDCA also probably acts partly by inhibiting hepatic cholesterol synthesis and perhaps by reducing intestinal cholesterol absorption. Reduction in dietary cholesterol is thought to possibly enhance its effect.

The changes in hepatic cholesterol metabolism do not result in altered serum cholesterol levels or changes in cholesterol pool sizes, but many studies have shown an approximate 20 % fall in serum triglyceride levels. However, this reduction has tended to diminish with continued treatment.

Exogenous CDCA is hepatotoxic in some animal species, including the rhesus monkey, rabbit, rat and baboon, but appears safe in the squirrel monkey and chimpanzee. Although occasional elevations in serum liver enzyme levels occur, no hepatotoxicity has been observed in man, probably because of a superior ability to excrete the toxic metabolite, lithocholic acid.