Ursosan

General characteristics. Structure:

Active agent: ursodezoksikholevy acid of 250 mg;

Excipients: starch corn — 49 mg; starch corn prezhelatinizirovanny — 24 mg; silicon dioxide colloid — 5 mg; magnesium stearate — 3,65 mg  

Capsule cover: gelatin — 98 mg; titanium dioxide — 2 mg.

Pharmacological properties:

Pharmacodynamics. Hepatoprotective means, renders also cholagogue, cholelitholytic, hypolipidemic, gipokholesterinemichesky and some immunomodulatory action.
Having high polar properties, ursodezoksikholevy acid (UDHK) is built in a membrane of a hepatocyte, a holangiotsit and an epithelial cell of a GIT, stabilizes its structure and protects a cell from the damaging effect of salts of toxic bile acids, reducing thus their cytotoxic effect. 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. Reducing concentration and stimulating the cholepoiesis rich with bicarbonates, UDHK effectively promotes permission of an intra hepatic cholestasia. At a cholestasia activates Sa2+-zavisimuyu alpha protease and stimulates an exocytosis, reduces concentration of toxic bile acids (chenodesoxycholic, lithocholic, deoxycholic) which concentration at patients with chronic diseases of a liver are increased.
Competitively reduces absorption of lipophilic bile acids in intestines, raises their fractional turn at enterogepatichesky circulation, induces a cholepoiesis, stimulates a passage of bile and removal of toxic bile acids through intestines. 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, increases in it concentration of bile acids, causes strengthening of gastric and pancreatic secretion, increases activity of a lipase, has hypoglycemic effect. Reduction of a saturation of bile cholesterol promotes its mobilization from gallstones what dissolution of cholesteric gallstones and the prevention of formation of new concrements is result of.
Immunomodulatory action is caused by oppression of an expression of histocompatibility antigens (HLA-1 — on membranes of hepatocytes and HLA-2 — on holangiotsita), normalization of a natural killerny lymphocyte activity, formation of SILT-2, reduction of quantity of eosinophils, suppression of immunocompetent Ig, first of all — IgM. Progressing of fibrosis detains. Regulates processes of apoptosis of hepatocytes, holangiotsit and epithelial cells of a GIT.

Pharmacokinetics. UDHK is absorbed in a small bowel due to passive diffusion (about 90%), and in an ileal gut — by means of active transport. Cmax is reached in 1–3 h and makes at intake 50 mg in 30, 60 and 90 min. — 3,8; 5,5 and 3,7 mmol/l respectively. Tmax is reached in 1–3 h. Linkng with proteins of plasma — to 96–99%. Gets through a placental barrier. At systematic administration of drug of UDHK becomes the main bile acid in blood serum. It is metabolized in a liver (clearance at primary passing through a liver) in taurinovy and glycine conjugates. The formed conjugates cosecrete in bile. About 50-70% of the general dose of drug are removed with bile. The insignificant quantity of not soaked up UDHK comes to a large intestine where is exposed to splitting by bacteria (7 dehydroxylation); the formed lithocholic acid partially is soaked up from a large intestine, sulphated in a liver and quickly removed in the form of a sulfolitokholilglitsinovy or sulfolitokholiltaurinovy conjugate.

Indications to use:

- uncomplicated cholelithiasis: biliary сладж; dissolution of cholesteric gallstones at the functioning gall bladder; prevention of a recurrence of a lithogenesis after a cholecystectomia;
- chronic hepatitises of various genesis (toxic, medicinal);
- cholestatic diseases of a liver of various genesis, including primary biliary cirrhosis, primary sclerosing cholangitis, cystous fibrosis (mucoviscidosis);
not alcoholic fatty alcoholic disease of a liver, including not alcoholic steatogepatit;
- alcoholic liver disease;
- viral hepatitis chronic;
- dyskinesia of biliary tract;
- biliary reflux gastritis and reflux esophagitis.

Route of administration and doses:

Inside, washing down with a small amount of water.
For dissolution of cholesteric gallstones an average daily dose of drug — 10–15 mg/kg. A course of treatment — 6–12 months and more before full dissolution of stones. At cholelithiasis all daily dose of drug is accepted once for the night.
For prevention of repeated formation of stones use of drug within several months after dissolution of stones is recommended.
After a cholecystectomia for prevention of a repeated cholelithiasis — on 250 mg 2 times a day within several months.
At chronic hepatitises of various genesis (toxic, medicinal), a chronic viral hepatitis, not alcoholic fatty alcoholic disease of a liver, including not alcoholic steatogepatit, an alcoholic liver disease, an average daily dose — 10–15 mg/kg in 2–3 receptions. Therapy duration — 6–12 months and more.

At cholestatic diseases of a liver of various genesis, including primary biliary cirrhosis, primary sclerosing cholangitis, cystous fibrosis (mucoviscidosis), an average daily dose — 12–15 mg/kg; if necessary the average daily dose can be increased to 20–30 mg/kg in 2–3 receptions. Therapy duration — from 6 months to several years.

At dyskinesia of biliary tract on hypokinetic type an average daily dose — 10 mg/kg in 2 receptions during of 2 weeks up to 2 months. If necessary the course of treatment is recommended to be repeated.

At biliary a reflux gastritis and a reflux esophagitis — on 250 mg/days before going to bed. A course of treatment — from 10–14 days to 6 months, if necessary — up to 2 years.

Calculation of daily number of capsules depending on the body weight of the patient and the recommended drug dose on 1 kg of body weight

Body weight, kg	The number of capsules at a dose
	10 mg/kg/days	12 mg/kg/days	15 mg/kg/days	20 mg/kg/days	30 mg/kg/days
19–25	1	1	2	2	3
26–30	1	1	2	2	4
31–35	1	2	2	3	4
36–40	2	2	2	3	5
41–45	2	2	3	4	5
46–50	2	2	3	4	6
51–55	2	3	3	4	7
56–60	2	3	4	5	7
61–65	3	3	4	5	8
66–70	3	3	4	6	8
71–75	3	4	5	6	9
76–80	3	4	5	6	10
81–85	3	4	5	7	10
86–90	4	4	5	7	11
91–95	4	5	6	8	11
96–100	4	5	6	8	12
101–105	4	5	6	8	13
106–110

Features of use:

At administration of drug for the purpose of dissolution of gallstones observance of the following conditions is necessary: stones have to be cholesteric (X-ray negative), their size should not exceed 15–20 mm, the gall bladder has to remain functioning and to be filled with stones no more than half, passability of a vesical and general bilious channel has to be kept.

At long (more than 1 month) administration of drug each 4 weeks in the first 3 months of treatment, further — each 3 months it is necessary to carry out biochemical analysis of blood for definition of activity of hepatic transaminases. Control of efficiency of treatment it is necessary to spend each 6 months according to ultrasonography of biliary tract. After full dissolution of stones it is recommended to continue use of drug within at least 3 months to promote dissolution of the remains of stones which sizes are too small for their detection, and prevention of a recurrence of a lithogenesis.

Side effects:

Diarrhea (can be dozozavisimy).
Seldom — calcination of gallstones, passing (tranzitorny) increase in activity of hepatic transaminases, nausea, vomiting, abdominal pain, allergic reactions.

Interaction with other medicines:

The antacids containing aluminum and ion-exchange resins (Colestyraminum) reduce absorption. Hypolipidemic HP (especially Clofibratum), are oestrogenic, Neomycinum or progestins increase bile saturation by cholesterol and can reduce ability to dissolve cholesteric bilious concrements.

Contraindications:

- hypersensitivity;
- X-ray positive (with the high content of calcium) gallstones;
- nonfunctioning gall bladder;
- the expressed renal failures, a liver, a pancreas;
- cirrhosis in a decompensation stage;
- acute infectious and inflammatory diseases of biliary tract.
- UDHK has no age restrictions to use, however children under 3 years are not recommended to use drug in this dosage form.

Use at pregnancy and feeding by a breast
Use of UDHK at pregnancy is possible only in that case when the expected advantage for mother exceeds potential risk for a fruit. Data on allocation of UDHK with breast milk are absent now. In need of use of UDHK in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Overdose:

Cases of overdose of drug are unknown.

Storage conditions:

In the dry, protected from light place, at a temperature of 15-25 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

50, 100 solid capsules.