BILE ACID THERAPY FOR GALLSTONES
Ursodiol (ursodeoxycholic acid) is a naturally occurring bile acidthat makes up less than 5% of the circulating bile salt pool in humans and a much higher percentage in bears. After oral admin-istration, it is absorbed, conjugated in the liver with glycine or taurine, and excreted in the bile. Conjugated ursodiol undergoes extensive enterohepatic recirculation. The serum half-life is approximately 100 hours. With long-term daily administration, ursodiol constitutes 30–50% of the circulating bile acid pool. A small amount of unabsorbed conjugated or unconjugated ursodiol passes into the colon, where it is either excreted or undergoes dehydroxylation by colonic bacteria to lithocholic acid, a sub-stance with potential hepatic toxicity.
The solubility of cholesterol in bile is determined by the relative proportions of bile acids, lecithin, and cholesterol. Although pro-longed ursodiol therapy expands the bile acid pool, this does notappear to be the principal mechanism of action for dissolution of gallstones. Ursodiol decreases the cholesterol content of bile by reducing hepatic cholesterol secretion. Ursodiol also appears to stabilize hepatocyte canalicular membranes, possibly through a reduction in the concentration of other endogenous bile acids or through inhibition of immune-mediated hepatocyte destruction.
Ursodiol is used for dissolution of small cholesterol gallstones in patients with symptomatic gallbladder disease who refuse chole-cystectomy or who are poor surgical candidates. At a dosage of 10 mg/kg/d for 12–24 months, dissolution occurs in up to 50% of patients with small (< 5–10 mm) noncalcified gallstones. It is also effective for the prevention of gallstones in obese patients undergoing rapid weight loss therapy. Several trials demonstrate that ursodiol 13–15 mg/kg/d is helpful for patients with early-stage primary biliary cirrhosis, reducing liver function abnormali-ties and improving liver histology.
Ursodiol is practically free of serious adverse effects. Bile salt-induced diarrhea is uncommon. Unlike its predecessor, chenode-oxycholate, ursodiol has not been associated with hepatotoxicity.