Ursosan

Ursosan reduces the production of cholesterol in the liver, as well as its absorption through the intestine. In addition, due to the formation of liquid complexes with cholesterol, this drug reduces the amount of cholesterol in the body and promotes their dissolution.

Indications of the ursosan

The medicine is prescribed in case of occurrence of cholesterol radiopaque stones in the gallbladder (under conditions of normal functioning of this organ, as well as with a stone size of max. 15 mm in diameter). Also, the drug is used in case of gastritis with concomitant bile reflux. Ursosan may be prescribed for symptomatic treatment in primary biliary cirrhosis (unless decompensated form of the disease is observed).

[1], [2]

Release form

Ursosan is available in capsules. One blister pack contains 10 capsules. In 1 packing there can be 1, 5 or 10 blisters.

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Pharmacodynamics

The drug is hepatoprotective - protects the liver function - and besides it has cholelitholitic, choleretic, as well as hypocholesterolemic and hypolipidemic effects. In addition, it performs some immunomodulatory functions.

Since ursodeoxycholic acid has strong polar properties, it is able to build into the membrane of cells and tissues of the digestive tract (such as cholangiocytes, hepatocytes, and epithelial cells), normalize their structure, and protect against bile acid salts with a toxic effect - reduce their cytotoxic impact. It also creates non-toxic mixed micelles in conjunction with bile acid, thereby reducing the ability of gastric contents to destroy membrane cells in diseases such as biliary reflux esophagitis. In addition, UDCA stimulates choleresis, that is, the release of bile by hepatocytes (simultaneously reducing its concentration), which contains a lot of bicarbonates, thereby eliminating intrahepatic cholestasis. This acid in cholestasis activates the alpha protease (Ca2 + -dependent), and also promotes exocytosis, reducing the level of bile acid concentrations that are toxic (such as deoxycholic, chenodeoxycholic, and lithocholic), which is increased due to chronic disorders in the functioning of the liver.

In the intestine, there is a decrease in the amount of absorbed lipophilic acids, their fractional turnover increases with portal-biliary circulation, as well as induction of choleresis, in which a bile passage occurs with the excretion of bile acid from the body through the intestine. After suppressing the intestinal absorption of cholesterol along with its synthesis in the liver, and besides this, reducing its release into bile, the level of saturation with this substance is reduced. The cholesterol solubility indices increase in this case, as a result of which liquid crystals appear. There is a decrease in the level of lithogenic bile index, and along with it, the bile acid saturation index is increased, as a result of which the process of pancreatic as well as gastric secretion intensifies, the activity of lipase production increases. As the cholesterol level decreases, it is better removed from the stones, and as a result, they dissolve better. In this way, the possibility of the formation of new stones in the hepato-biliary system is prevented.

The immunomodulatory effect of the drug is due to the suppression of the expression of histocompatibility antigens (in the walls of hepatocytes (type HLA-1) and also of cholanocytes (type HLA-2)), stabilization of EK / T-lymphocyte activity, decrease in the number of eosinophils, IL-2 production, oppression immunocompetent cells (primarily IgM). There is a delay in the development of fibrosis.

Pharmacokinetics

UDCA is absorbed through the small intestine through passive transport (approximately 90%), and through the ileum through active transport. The maximum possible concentration is reached after 1-3 hours. After internal reception of 50 mg after half an hour / 1 hour / 1.5 hours, the parameters are 3.8 / 5.5 / 3.7 mmol / l, respectively. Time to reach the maximum possible concentration is 1 to 3 hours. With plasma proteins binds to 96-99%. Passes through the placental barrier. If Ursosan is taken systematically, UDC acid will become the main bile acid in the blood serum. When splitting in the liver is converted into taurine conjugate and salicylic acid, after which these elements are released into bile. Along with it, about 50-70% of the medicine is excreted. The remainder of unabsorbed UDCA enters the large intestine, where it is cleaved by bacteria (during 7-dehydroxylation). The resulting lithocholic acid is fragmentarily absorbed from the large intestine and sulphated through the liver, after which it is excreted as a sulfolithochololtaurine or sulfolitocholylglycine compound.

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Dosing and administration

The drug is administered orally, it is not recommended to chew the capsules before taking it or crush it in other ways. Usually the daily intake is taken at a time - it is best to use it before bed, while washing with water. Dosage, as well as the duration of the treatment course should be determined by the attending physician.

If the patient has cholesterol gallstones, the daily dosage is usually deduced from the calculation of 10 mg of the drug per 1 kg of weight. The course of treatment lasts from six months to 2 years, but if improvement (reduction in the size of the stones) is not observed within the first year after the start of taking the drug, therapy should be discontinued.

At the initial stage of treatment, it is necessary to check the activity of liver transaminases every month. Also, you should monitor the change in the size of the stones - through cholecystography or ultrasound (at least once every six months). In addition, during the therapy, it is necessary to perform examinations in order to be able to detect the beginning of the calcification of stones in time (if calcified stones are found in the gall bladder, Ursosan's treatment stops).

With chemo-toxic reflux gastritis (C), the drug is usually given in a dosage of 1 capsule / day. The therapeutic course usually lasts 10-14 days.

With PBC liver dosage of the drug is usually 14 mg / 1 kg of weight per day. At the initial stage of treatment, the daily dose is divided into 3 separate doses (as the dose can not be evenly divided, because in one capsule the drug contains 250 mg of UDCA, most of the drug is recommended to be drunk in the evening).

The treatment course with the use of Ursosan with PBC liver can have unlimited duration. Sometimes at the initial stage of treatment the clinical manifestations of the disease worsen - if this happened, you should reduce the daily dose of the drug to 1 capsule, gradually increasing it to the required amount (add 1 capsule each new week).

[10], [11]

Use of the ursosan during pregnancy

The drug should not be taken on the 1st trimester of pregnancy. Ursosan can be administered at the 2nd or 3rd trimester, but only for life indications. Before starting treatment with UDCA, a woman who is of childbearing age should completely eliminate the risk of pregnancy for the period of therapy, using reliable contraceptive methods.

Contraindications

Ursosan is contraindicated in case of hypersensitivity to UDCA, as well as additional capsule elements.

The medicine is not prescribed if the patient has inflammation of the gallbladder or its ducts (in acute form), blockage of the bile ducts, or problems with the contractile capacity of the gallbladder.

The drug is not used in the treatment of patients with biliary colic, calcified gallstones, as well as those who can not visualize the gallbladder by radiological methods.

Contraindications are violations in the liver and kidneys, as well as children under 5 years.

With caution should be taken to patients who have the following diseases: ulcer, hepatitis or cirrhosis, extrahepatic cholestasis, as well as inflammatory processes in the intestine.

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Side effects of the ursosan

Among the side effects of the medication Ursosan:

Gastrointestinal organs, as well as the hepatobiliary system: pain in the liver (usually appear in people with PBC liver), diarrhea, transient increase in transaminase activity, calcification of gallstones, and vomiting. In patients suffering from PBC, liver cirrhosis can go into a decompensated stage with partial progress after completion of treatment.

At the beginning of medical therapy, urticaria can be observed.

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Overdose

In case of an overdose, Ursosan develops diarrhea. To treat the symptom, there is no specific drug - if an overdose occurs, the dose of the drug should be reduced. If this does not help to get rid of discomfort, you need to cancel the medication and perform procedures that restore the balance of water and salt in the body.

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Interactions with other drugs

Taking the drug in combination with colestyramine, colestipol, as well as antacid agents (which contain substances such as aluminum oxide and hydroxide, as well as magnesium silicate) can reduce UDCA absorption. If these medications still need to be taken together, you should consume them with at least a 2-hour interval.

With simultaneous reception with cyclosporine, there is an increase in the intestinal absorption of this substance. Therefore, you need to closely monitor the amount of cyclosporine in the plasma and adjust its dosage, if necessary.

There may be a decrease in ciprofloxacin absorption when combined with UDCA.

Ursosan stimulates the production of cytochrome P450 3A, and is also able to change the concentration of drugs that are metabolized by this enzyme in plasma. Combining the intake of this drug with the use of dapsone and nitrendipine, you need to monitor the dosage of the latter.

At simultaneous reception with a probucolum, klofibratom, and also bezafibrate the efficiency of treatment with use UDCA decreases.

Efficacy of Ursosan is reduced if taken in combination with estrogens, as well as oral contraceptives. In addition, its effect is reduced if the drug is taken by a patient who observes a diet with high cholesterol and vice versa a low-fiber diet.

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Storage conditions

The medicine should be stored in a temperature of 15-25 ° C.

Shelf life

Ursosan is allowed to use for 4 years from the date of release.