Ursodezoksikholevy acid

General characteristics. Structure:

Active ingredient: 150 mg, 250 mg or 300 mg of ursodezoksikholevy acid in 1 capsule. 

The drug rendering cholelitholytic, cholagogue, gepatoprotektivny, gipokholesterinemichesky, immunomodulatory action.

Pharmacological properties:

Pharmacodynamics. Stabilizes membranes of hepatocytes and holangiotsit, has direct cytoprotective effect. As a result of action of HP the content of hydrophobic (potentially toxic) acids decreases by gastrointestinal circulation of bile acids. Due to reduction of absorption of cholesterol in intestines and other biochemical effects has gipokholesterinemichesky effect. Suppresses the death of cells caused by toxic bile acids.

Having high polar properties, ursodeoksikholevy acid (UDHK) forms the non-toxic mixed micelles with non-polar (toxic) bile acids that reduces ability of a gastric reflyuktat to damage cellular membranes at biliary a reflux gastritis and a reflux esophagitis. Besides, UDHK forms the double molecules capable to be included cellular membranes, to stabilize them and to do unreceptive to action of cytotoxic micelles. Reduces a bile saturation cholesterol due to oppression of its absorption in intestines, suppression of synthesis in a liver and decreases in secretion in bile; increases solubility of cholesterol in bile, forming with it liquid crystals; reduces a litogenny index of bile. Dissolution of cholesteric gallstones (a consequence of change of a ratio cholesterol / bile acids in bile) and the prevention of formation of new concrements (result of reduction of content in cholesterol bile) is result. Induces the cholepoiesis rich with bicarbonates that leads to increase in a passage of bile and stimulates removal of toxic bile acids through intestines.

Immunomodulatory action is caused by oppression of an expression of HLA antigens on membranes of hepatocytes and holangiotsit, normalization of a natural killerny lymphocyte activity, etc. Authentically progressing of fibrosis at patients with primary biliary cirrhosis, a mucoviscidosis and alcoholic steatogepatit detains, reduces risk of development of a varicosity of a gullet.

Pharmacokinetics. At intake it is absorbed in a jejunum due to passive diffusion, and in an ileal gut by means of active transport. Cmax is reached in 1–3 h. Linkng with proteins high (at healthy volunteers at least 70% of not conjugated UDHK are connected with proteins). At systematic reception of UDHK becomes the main bile acid in blood serum and makes about 48% of total quantity of bile acids in blood. Joins in system of gastrointestinal circulation. In a liver of UDHK contacts glycine and taurine; the formed conjugates cosecrete in bile. The therapeutic effect depends on concentration of UDHK in bile; against the background of therapy there is a dozozavisimy increase in its share in a bullet of bile acids up to 50–75% (at daily doses of 10-20 mg/kg). Passes through a placental barrier. Very small quantity (less than 1%) — with urine is removed preferential with excrements. The insignificant quantity of not soaked up UDHK in a large intestine is exposed to splitting by bacteria (7 dehydroxylation) to lithocholic acid which is partially soaked up from a large intestine, is sulphated in a liver and quickly removed with excrements in the form of sulfotilkholilglitsinovy or sulfotilkholiltaurinovy conjugates.

Indications to use:

Cholesteric stones in a gall bladder, hepatitis (chronic, including atypical forms chronic autoimmune, acute virus), not alcoholic steatogepatit, toxic (including alcoholic, medicinal) damages of a liver, primary biliary cirrhosis and a mucoviscidosis of a liver, primary sclerosing cholangitis, an atresia of intra hepatic bilious ways, a cholestasia at parenteral food, dyskinesia of biliary tract, a biliary reflux gastritis and a reflux esophagitis; chronic opisthorchosis; prevention of injuries of a liver when using hormonal contraceptives and tsitostatik.

Route of administration and doses:

Inside (without chewing and washing down with enough liquid). The mode of dosing and duration of treatment are established individually; average dose of 8-10 mg/kg/days.

Features of use:

Use at pregnancy and feeding by a breast. At pregnancy it is possible if the expected effect of therapy exceeds potential risk for a fruit (adequate and strictly controlled researches of safety of use for pregnant women were not conducted). The feeding women need care at appointment (it is unknown whether the HP gets into breast milk).

At long (more than 1 month) treatment monthly control of level of hepatic transaminases, ShchF, gamma глутамилтрансферазы and bilirubin in blood is necessary (especially in the first 3 months of therapy). Efficiency of treatment has to be confirmed by X-ray inspection and ultrasonography of biliary tract (each half a year). For the purpose of prevention of a recurrence of a cholelithiasis it is necessary to continue treatment some more months after dissolution of stones.

During treatment women of childbearing age should apply reliable methods of contraception.

Special instructions. Positive results can be received only in the presence of purely cholesteric (X-ray negative) gallstones no more than 15-20 mm in size, at the kept function of a gall bladder and passability vesical and the general bilious channels.

Side effects:

Diarrhea or lock, nausea, pain in epigastric area and the right hypochondrium, calcination of gallstones, increase in activity of hepatic transaminases, allergic reactions (rashes and a skin itch). At treatment of primary biliary cirrhosis the passing decompensation of cirrhosis which disappears after cancellation of HP can be observed.

Interaction with other medicines:

Aluminum-bearing antacids, Colestyraminum and колестипол connect ursodeoksikholevy acid in intestines, reduce its absorption and weaken efficiency. Hypolipidemic HP (especially Clofibratum), are oestrogenic, Neomycinum, progestins can increase bile saturation by cholesterol and reduce ability of UDHK to dissolve cholesteric bilious concrements.

Contraindications:

Hypersensitivity, acute inflammatory diseases of a gall bladder, bilious channels and intestines, full obstruction of bilious ways, calciphied gallstones, cirrhosis in decompensation stages, the expressed renal failures, a pancreas.

Restrictions to use. Children's age (the corresponding researches of cholelitholytic effect of UDHL of age at children are not conducted). Researches at children with cholestatic a disease of a liver and an atresia of bilious channels did not reveal specific pediatric problems which would limit use of HP at children.

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Capsules of 150 mg, 250 mg or 300 mg. On 10 capsules in each blister, on 3, 6 or 10 blisters together with the application instruction in cardboard packaging.