Гепавилаг

General characteristics. Structure:

Active agent: 1 g of a L-leucine, 0,5 g of L-valine, 0,5 L-izoleytsina, 0,418 g of L-arginine of a hydrochloride, 0,084 g of glycylglycine.

Excipients: citric acid monohydrate (Е 330); aspartame (Е 951); K-25 povidone, AN 1405 Lemon fragrance, maltodextrin.

Pharmacological properties:

Pharmacodynamics. Гепавилаг contains three irreplaceable L-leucine amino acids, L-valine, L-izoleytsin necessary for synthesis of a number of proteins and other biologically important components, one replaceable amino acid - L-arginine and dipeptide glycylglycine.

On structure branched amino acids which provide stabilization of exchange of aromatic amino acids prevail, have positive effect on exchange of proteins in muscles, a liver and neurotransmitters in the central nervous system. Researches in the field of compensation of a malnutrition as risk factor of progressing of cirrhoses, showed that at successful compensation of a malnutrition with use of branched irreplaceable amino acids it is possible to achieve decrease in a lethality at liver cirrhoses. Usual states at which branched irreplaceable amino acids are used are states with negative nitrogenous balance, states with metabolic tension (hypermetabolism), states with an intolerantnost to proteins (liver cirrhoses). The protective effect of branched irreplaceable amino acids on development of a sakropeniya in persons of advanced and senile age is established.

Researches at patients with liver cirrhoses at infusional administration of amino acids with a branched side chain showed that there is an increase in content in blood of the entered amino acids and reduction of aromatic amino acids and methionine, at the same time improvement of indicators of hepatic encephalopathy and the electroencephalogram is noted. From five amino acids of drug of Gepavilag, according to the researches in vitro on skeletal muscles, it is shown that the leucine, first of all, is responsible for induction of synthesis of protein.

The stimulating effect of a leucine on synthesis of protein is established through induction of broadcast of MRNK. At the same time there is a set of additional mechanisms, including phosphorylation of ribosomal protein, activation of a kinase of S6, factor of initiation (elF) 4E. A key component in this process and the phosphorylation accompanying it, at mammals is alarm protein switch, the called mTOR (mammalian target of rapamycin). It is revealed that amino acids with a branched side chain, unlike other hydrophobic amino acids, are capable to provide the need for maintenance of structure of protein and promote reduction of speed of degradation of proteins, keeping their native structure. Moreover, amino acids with a branched side chain reduce proteolysis of proteins and their effect, apparently, is connected with insulinopodobny action on atrogin-1 (atrogin-1).

Pharmacokinetics. The L-leucine, L-valine and L-izoleytsin and arginine at intake are well soaked up from a GIT (bioavailability makes more than 96%). Amino acids at first get into a portal vein of a liver, and only then in a system blood stream. From intravascular space of amino acid are redistributed in intercellular liquid and are transferred in cells of different fabrics. Assessment of pharmacokinetics of amino acids with a branched side chain on the oxidation level of marked phenylalanine showed that the most optimum is joint administration of three amino acids of valine, a leucine and isoleucine. At the same time it is revealed that high concentration of a leucine in blood are followed by reduction of concentration of valine and an isoleucine, in combination with activation of the corresponding dehydrogenases. Concentration of free amino acids in a blood plasma and fabrics are regulated by endogenous mechanisms in the narrow range which depends on age, a condition of food and a clinical condition of the patient.

Biotransformation. The first stages in a catabolism of amino acids with a branched side chain are the general for three amino acids, through the corresponding aminotrasferaza and dehydrogenases, with formation of their keto-derivative (BCKD). At the same time both cytosolic, and mitochondrial isoenzymes аминотрасфераз are identified. Their further metabolism differs and characterized, first of all, by different education level of end products (glucose and/or ketonic bodies). The catabolism of amino acids with a branched side chain is specifically regulated by allosteric and covalent mechanisms. BCKD inhibit phosphorylation and activate dephosphorylation that is the cornerstone of their impact on membrane structures in cells. BCKD have the following distribution on degree of metabolic activity: their greatest part is the share of skeletal mshshcha (60-70%) and fatty tissue (15-20%) and very small part is concentrated in a liver (about 10%). Arginine is metabolized in a liver, as a result of hydrolysis urea and ornithine are formed.

Distribution. At administration of mix of valine, a leucine and isoleucine these amino acids, and first of all a leucine collect preferential in skeletal muscles and a liver. However, in 4 hours after intravenous administration of 60% of a leucine it is completely metabolized and products of metabolism are defined in the exhaled CO2.

Removal. At administration of amino acids with a branched side chain absolute excretion of amino acids changes in the direction from big sizes to smaller among amino acids as follows: arginine, valine, isoleucine and leucine. Surplus of a L-leucine, L-valine and L-izoleytsina is removed by kidneys in not changed look. Arginine is emitted during glomerular filtering and almost reabsorbirutsya completely in kidneys. The glycylglycine pharmacokinetics is in detail not studied.

Indications to use:

Гепавилаг apply as a source of the branched amino acids necessary for synthesis of biologically important components which deficit is noted at chronic diffusion diseases of a liver and other states with catabolic options of metabolism.

Route of administration and doses:

Inside, previously having dissolved package contents in 100-150 ml of boiled water. The daily dose for adults makes 12-15 g of granulate (4-5 packages), divided into 2-3 receptions. At patients with the increased need for amino acids use of drug in higher doses of 18-24 g of granulate is allowed that corresponds to 6-8 packages of medicine. Duration of a course of treatment makes not less than 30 days.

Features of use:

Special precautionary measures at use of medicine of Gepavilag are not required. Drug does not influence speed of psychomotor reactions and to ability to manage transport and other mechanisms.

Pregnancy and feeding by a breast. Now objective data on efficiency and safety of use of drug of Gepavilag during pregnancy and in the period of a lactation are absent, in this regard the specified medicine is not recommended to be applied at pregnant women. For treatment it is necessary to stop breastfeeding.

Side effects:

At use of drug of Gepavilag in compliance with indications and recommendations about a dosage, by-effects arise seldom. Nausea, vomiting, inflows of heat and perspiration is occasionally noted. Hypersensitivity reactions are possible.

Interaction with other medicines:

Now there are no data on any medicinal interactions at simultaneous use of drug of Gepavilag with other medicines, and also data on interaction between drug components as a part of a dosage form.

Contraindications:

Use of medicine of Gepavilag is contraindicated at patients with vrolodenny disturbances of metabolism of amino acids, irreversible damages of kidneys with uraemia. Now objective data on efficiency and safety of use of drug of Gepavilag during pregnancy and in the period of a lactation are absent, in this regard the specified medicine is not recommended to be applied at pregnant women. For treatment it is necessary to stop breastfeeding.

Children. Because of insufficient experience of use of Gepavilag it should not be used at children.

Overdose:

The phenomena of overdose it is not established.

Storage conditions:

In the place protected from moisture and light at a temperature not above 25 °C. Period of validity 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

Without recipe

Packaging:

On 3 g in packages from the material combined for packaging of foodstuff. On 20 packages together with the application instruction place in a pack from a cardboard.