Disease relevance of Ursolvan

• For gallstone dissolution study, additional groups of mice that have formed gallstones were fed chow with or without 0.5% beta-muricholic acid or UDCA for 8 weeks [1].
• Ursodesoxycholic acid, widely used for the treatment of cholestatic liver disease, causes choleretic, anti-apoptotic and immunomodulatory effects [2].
• Preventive treatment with ursodesoxycholic acid could be considered in patients with meconium ileus [3].
• Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration [4].
• Ursodesoxycholic acid: effect on xanthomas in Alagille-Watson syndrome [5].
• The increased risk of primary liver cancer in ursodeoxycholic acid-treated patients was 3-fold (HR, 3.17; 95% CI, 0.64-15.62), in contrast to an 8-fold increase in those not treated (HR, 7.77; 95% CI, 1.30-46.65) [6].

High impact information on Ursolvan

• We conclude that beta-muricholic acid is more effective than UDCA in treating or preventing diet-induced or experimental cholesterol gallstones in mice [1].
• AIM: To determine the pharmacokinetics and bioequivalence of a new liquid formulation of ursodeoxycholic acid (Ursofalk suspension) with a standard capsule (Ursofalk) in a randomized, unblinded, crossover designed study of 24 healthy adults [7].
• Bioequivalence of a new liquid formulation of ursodeoxycholic acid (Ursofalk suspension) and Ursofalk capsules measured by plasma pharmacokinetics and biliary enrichment [7].
• CONCLUSIONS: The significantly higher AUC and Cmax and shorter Tmax for the Canadian Ursofalk tablets compared to the UDCA capsule preparations supports better bioavailability [8].
• With the administration of ursodeoxycholic acid (UDCA) to patients with ICP, pruritus and serum liver values are improved, the concentration of bile acids in blood is diminished and the proportion of their conjugated metabolites returned to normal [9].

Chemical compound and disease context of Ursolvan

• The appearance of iso-ursodeoxycholic acid (isoUDCA; 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acid) in serum of patients with chronic cholestatic liver disease and of healthy subjects during administration of ursodeoxycholic acid (UDCA) is reported [10].
• Our recent studies demonstrated the potential for N-nitroso conjugate formation from ursodeoxycholic acid, a 7 beta-epimer of chenodeoxycholic acid used as a drug Actigall to dissolve gallstones [11].
• Supportive therapy, including pulse therapy with 1g methylprednisolone for 3 days, ursodesoxycholic acid, branched-chain amino acid, and azathioprine did not resolve the hepatic failure [12].

Biological context of Ursolvan

• Biotransformation of the methyl derivatives of UDCA occurred mainly by conversion to more polar glucuronide conjugates [13].
• The relationship of liver regeneration to immunoactivity was examined after ursodesoxycholic acid (UDCA) administration to partially (about 66%) hepatectomized rats [14].
• Tamoxifen may exert this effect, which warrants further study, either via cholangiocyte estrogen receptors, inhibiting cholangiocyte proliferation and inducing apoptosis or by activating pregnane X receptor, analogous to the mode of action of UDCA [15].

Anatomical context of Ursolvan

• Because ursodesoxycholic acid exists in the bile juice, these results suggest that the hepatic vagus nerve is specifically active with endogenous bile acids in the control of liver regeneration [16].
• In isolated hamster hepatocytes, the Ca2+ ionophore A-23187 immediately decreased the uptake rate of taurocholic acid (TCA) by 60-70%, whereas it slowly inhibited that of ursodeoxycholic acid (UDCA) by a maximum of 35-45%, with an inhibition constant (Ki) of 0.36 and 1.93 microM, respectively [17].
• Orally administered gallbladder therapeutic agents, Part II: Actigall (ursodeoxycholic Acid, UDCA) [18].

Associations of Ursolvan with other chemical compounds

• While there is effective treatment for AIH (steroids with or without azathioprine) and PBC (Ursodesoxycholic acid) no such treatment is currently established for PSC [19].
• In conclusion, administration for 2 wk of TUDCA, compared with an equimolar amount of unconjugated UDCA plus taurine, produced in the bile of hamsters a higher percentage of UDCA, a lower glycine-to-taurine ratio of UDCA conjugates, and a lower saturation index before and after adjustment for UDCA-rich bile [20].

Gene context of Ursolvan

• Feeding of ursodeoxycholic and iso-ursodeoxycholic acid markedly down-regulated alpha2-macroglobulin and TIMP-1 expression in cholestasis but did not affect overexpression of beta-fibrinogen and haptoglobin [21].

Analytical, diagnostic and therapeutic context of Ursolvan

• In three patients, neuropathy improved with interferon alpha, interferon alpha + ursodesoxycholic acid, or steroids + plasma exchange [22].
• With residual gallstones, the risk of biliary symptoms developing was significantly lower in patients with a < or = 3 mm fragment size at the end of ESWL treatment and in those treated consistently with UDCA for 6 months or more after treatment with ESWL [23].
• It was also noted that hepatic branch vagotomy or ursodesoxycholic acid or both did not affect serum parameters indicating liver and kidney function [16].
• When ursodesoxycholic acid 12.5 mg kg(-1) day(-1) was administered orally, a significant increase in the mitotic index was observed 2 and 3 days after hepatectomy, and the mitotic index response 2 days after hepatectomy was dose-dependent in the range of 0-25 mg kg(-1) day(-1) [16].
• Plasma concentrations of UDCA were determined in six healthy volunteers after oral administration of tablets containing the inclusion complex or UDCA alone (Ursacol) [24].

References