Disease relevance of ursodiol

• In the treatment of gallstones with extracorporeal shock-wave lithotripsy, the bile acid ursodiol is administered to dissolve the gallstone fragments [1].
• A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group [2].
• CONCLUSIONS: In a group of patients with well-defined primary sclerosing cholangitis, ursodiol provided no clinical benefit [3].
• We randomly assigned 145 patients with biopsy-proved primary biliary cirrhosis to receive ursodiol (13 to 15 mg per kilogram of body weight per day) (72 patients) or placebo (73 patients) [4].
• Follow-up analysis of 95 liver-biopsy specimens showed a significant improvement in the mean histologic score (P less than 0.002) and in all the characteristic histologic features except fibrosis only in the group given ursodiol [2].

High impact information on ursodiol

• Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group [3].
• Abdominal pain after taking ursodiol [5].
• On the basis of an intention-to-treat analysis of all 600 patients, 21 percent receiving ursodiol and 9 percent receiving placebo (P less than 0.0001) had gallbladders that were free of stones after six months [1].
• On ursodiol therapy, hepatic bile acid synthesis was enhanced 2-fold compared with controls, and microscopy revealed chronic hepatitis without cholestasis [6].
• Treatment with ursodiol, a more hydrophilic bile acid, improved pruritus, produced 37% weight gain, and after 2 years reduced serum primary bile acid concentrations about 85%, while accounting for 71% of serum and 24% of biliary bile acid conjugates [6].

Chemical compound and disease context of ursodiol

• Lithotripsy plus ursodiol is superior to ursodiol alone for cholesterol gallstones [7].
• Methotrexate improves biochemical tests in patients with primary biliary cirrhosis who respond incompletely to ursodiol [8].
• The association between dysplasia and ursodiol use remained after adjustment for sex, age at onset of colitis, duration of colitis, duration of sclerosing cholangitis, severity of liver disease, and sulfasalazine use (adjusted odds ratio, 0.14 [CI, 0.03 to 0.64]; P = 0.01) [9].
• Cholesterol gallstones in a functioning gallbladder will dissolve slowly when the secretion of unsaturated bile is induced by the ingestion of ursodiol or chenodiol, which are naturally occurring bile acids [10].
• In patients with primary biliary cirrhosis (PBC), ursodeoxycholic acid (ursodiol) improves laboratory test markers of cholestasis and hepatic inflammation as well as some hepatic histological features; it also delays histological progression in the early stages of PBC [11].

Biological context of ursodiol

• Histology was favorably affected by ursodiol in patients in strata 1 and 2 but not in strata 3 and 4 [12].
• There were no differences in peak concentration, time to peak, area under the serum concentration versus time curve, or bioavailability of oral cyclosporine when administered alone or with ursodiol [13].
• RESULTS: There was no significant effect of ursodiol on CsA absorption: AUC was 5011 vs 5486 ng.h.ml-1, Cmax was 832 vs 871 ng.ml-1 and tmax was 2 vs 2 h, after ursodiol and placebo, respectively [14].
• It was successfully applied to the pilot bioequivalence study of Ursodiol in male human subjects [15].

Anatomical context of ursodiol

• Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow transplantation. A randomized, double-blind, placebo-controlled trial [16].
• Drug-induced vanishing bile duct syndrome: response to ursodiol [17].
• RESULTS: Addition of Ursodiol to high-dose IBU and normal doses of PE showed a significant reduction in the percentage of rats with ulcers (P < 0.05), total number of serositis events (P < 0.01), total number of severe ulcers (P < 0.001), and an absence of ulcers in the large intestine [18].
• The mechanisms by which ursodiol apparently directly stimulates the LDL receptor remain speculative but may involve alteration of cell membrane fluidity, change in the rate of LDL receptor cycling, and increase in the number of LDL receptors [19].

Associations of ursodiol with other chemical compounds

• The hypothesis of diameter decrease proportional to treatment time was tested with data from 223 patients with radiolucent gallbladder stones up to 20 mm in diameter treated with 7-8 or 14-15 mg.kg-1.day-1 of either ursodiol or chenodiol for 1 year, followed up after 3, 6, and 12 months of treatment [20].
• Liver biopsy was performed at the beginning and at the end of treatment and was evaluated blindly by our pathologist (F.C.). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamyltransferase (GGT) levels were significantly reduced by 25% from baseline values during treatment with ursodiol but not with placebo [21].
• Oral administration of ursodeoxycholic acid (ursodiol) shifted the cholesterol composition of the bile from a supersaturated, potentially crystallized state to a liquid (micellar) state [22].
• A suspension was prepared by opening commercially available 300-mg capsules of ursodiol, adding Glycerin, USP, to form a paste, and then adding Simple Syrup, NF [23].
• S-Allylcysteine was only active for the growth inhibition endpoint, and DFMO, Iycopene, perillyl alcohol, ursodiol, and black tea polyphenols were only active for the involucrin endpoint [24].

Gene context of ursodiol

• Abnormal hepatic sinusoidal bile acid transport in an Amish kindred is not linked to FIC1 and is improved by ursodiol [6].
• Thus, differences in ursodiol enrichment of the bile acid pool do not explain better responses of laboratory tests and histology found in patients with less advanced PBC [12].
• Ursodiol use is possibly associated with lower incidence of hepatocellular carcinoma in hepatitis C virus-associated liver cirrhosis [25].
• However, mean baseline AST levels were significantly higher in the ursodiol group, 28.0 U/l vs 18.1 U/l in the control group (p = 0.001) [26].
• A Medstone STS lithotripter was used together with ursodiol [27].

Analytical, diagnostic and therapeutic context of ursodiol

• Long-term ursodiol therapy slows the progression of primary biliary cirrhosis and reduces the need for liver transplantation [4].
• There was no significant difference between the groups in time to treatment failure (relative risk of treatment failure in the ursodiol group, 1.01; 95 percent confidence interval, 0.6 to 1.7) [3].
• In four of the five patients treated with 600 to 900 mg of ursodiol two to three times daily, results of liver-function tests returned to normal [28].
• METHODS: From May 1989 to July 1995, we enrolled 105 patients with well-documented primary sclerosing cholangitis in a randomized, double-blind study comparing ursodiol (13 to 15 mg per kilogram of body weight per day in divided doses) with placebo [3].
• At 10 centers, 600 symptomatic patients with three or fewer radiolucent gallstones 5 to 30 mm in diameter, as visualized by oral cholecystography, were randomly assigned to receive ursodiol or placebo for six months, starting one week before lithotripsy [1].

References