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Absorbed 7-keto-lithocholic acid is stereospecifically reduced in the liver to chenodiol. Lithocholic acid causes cholestatic liver injury and can cause death from liver failure in certain species unable to form sulfate conjugates. Lithocholic acid is formed by 7-dehydroxylation of the dihydroxy bile acids (ursodiol and chenodiol) in the gut lumen. The 7-dehydroxylation reaction appears to be alpha-specific, i. Man has the capacity to sulfate lithocholic acid. Although liver injury has not been associated with ursodiol therapy, a reduced capacity to sulfate may exist in some individuals, but such a deficiency has not yet been clearly demonstrated. Ursodiol suppresses hepatic synthesis and secretion of cholesterol, and also inhibits intestinal absorption of cholesterol. It appears to have little inhibitory effect on synthesis and secretion into bile of endogenous bile acids, and does not appear to affect secretion of phospholipids into bile, buy ultima deca 500 mg injectable steroids deca durabolin, deca. With repeated dosing, bile ursodeoxycholic acid concentrations reach a steady-state in about 3 weeks. Although insoluble in aqueous media, cholesterol can be solubilized in at least two different ways in the presence of dihydroxy bile acids. In addition to solubilizing cholesterol in micelles, ursodiol acts by an apparently unique mechanism to cause dispersion of cholesterol as liquid crystals in aqueous media. Thus, even though administration of high doses (e. The overall effect of ursodiol is to increase the concentration level at which saturation of cholesterol occurs. The various actions of ursodiol combine to change the bile of patients with gallstones from cholesterol-precipitating to cholesterol-solubilizing, thus resulting in bile conducive to cholesterol stone dissolution. After ursodiol dosing is stopped, the concentration of the bile acid in bile falls exponentially, declining to about 5% to 10% of its steady-state level in about 1 week. On the basis of clinical trial results in a total of 868 patients with radiolucent gallstones treated in 8 studies (three in the U. With an ursodiol dose of about 10 mg/kg/day, complete stone dissolution can be anticipated in about 30% of unselected patients with uncalcified gallstones 20 mm in maximal diameter rarely dissolve their stones. The chance of gallstone dissolution is increased up to 50% in patients with floating or floatable stones (i. Stone recurrence after dissolution with ursodiol therapy was seen within 2 years in 8/27 (30%) of patients in the U. Of 16 patients in the U. Stone recurrence has been observed in up to 50% of patients within 5 years of complete stone dissolution on ursodiol therapy. Serial ultrasonographic examinations should be obtained to monitor for recurrence of stones, bearing in mind that radiolucency of the stones should be established before another course of ursodiol is instituted. A prophylactic dose of ursodiol has not been established. Two placebo-controlled, multicenter, double-blind, randomized, parallel group trials in a total of 1,316 obese patients were undertaken to evaluate ursodiol in the prevention of gallstone formation in obese patients undergoing rapid weight loss. The first trial consisted of 1,004 obese patients with a body mass index (BMI) ? 38 who underwent weight loss induced by means of a very low calorie diet for a period of 16 weeks.
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