Ornithine - instructions for use, doses, side effects, contraindications, price, where to buy - geotar medicinal directory. Experience with the use of the oral form of L-ornithine-L-aspartate in hyperammonemia in patients with chronic liver diseases on

Gross formula

Pharmacological group of the substance Ornithine

Nosological classification (ICD-10)

CAS code

Characteristics of the substance Ornithine

Colorless crystals. Easily soluble in water, alcohol, slightly soluble in ether.

Pharmacology

It has a hypoammoniemic effect. Utilizes ammonium groups in the synthesis of urea (ornithine cycle). Reduces the concentration of ammonia in the blood plasma, helps to normalize the acid-base balance of the body and the production of insulin and growth hormone. Improves protein metabolism in diseases requiring parenteral nutrition.

When ornithine is ingested, aspartate dissociates into its constituent components (ornithine and aspartate), which are absorbed into small intestine by active transport through the intestinal epithelium.

It is excreted in the urine through the urea cycle.

Application of the substance Ornithine

Hyperammonemia, hepatitis, liver cirrhosis, hepatic encephalopathy (latent and severe), incl. as part of complex therapy in violation of consciousness (precoma or coma); as a corrective additive to preparations for parenteral nutrition in patients with protein deficiency.

Contraindications

Hypersensitivity expressed kidney failure(creatinine concentration more than 3 mg/100 ml).

Use during pregnancy and lactation

During pregnancy, it is possible only under the strict supervision of a doctor. Stop during treatment breast-feeding.

Side effects of Ornithine

Dermal allergic reactions, nausea, vomiting.

Interaction

Pharmaceutically incompatible with penicillin, vitamin K, rifampicin, meprobamate, diazepam, phenobarbital, ethionamide.

Routes of administration

Inside, in / in, in / m.

Ornithine Precautions

Use with caution by drivers Vehicle and people whose work requires a quick mental and physical reaction, and is also associated with increased concentration.

If nausea or vomiting occurs, the rate of administration of the drug should be reduced.

Interactions with other active substances

Trade names

Included in medications

A.05.B.A.06 Ornithine oxoglurate

IV.E40-E46.E46 Protein-energy malnutrition, unspecified

XI.K70-K77.K72 Liver failure not classified elsewhere

IV.E70-E90.E72.2 Urea cycle metabolic disorders

XI.K70-K77.K74 Fibrosis and cirrhosis of the liver

XI.K70-K77.K76.9 Liver disease, unspecified

Preparation f pharmaceutically incompatible(R Solutions must not be mixed in the same syringe)with vitamin K, benzathine benzylpenicillin, diazepam, meprobamate, phenobarbital, rifampicin, ethionamide.

Gross formula

Pharmacological group of the substance Arginine aspartate

Nosological classification (ICD-10)

CAS code

Characteristics of the substance Arginine aspartate

Amino acid, dietary supplement. White crystalline, odorless, water-soluble powder.

Pharmacology

Increases endurance. It activates cellular metabolism, urea metabolism, promotes the neutralization and excretion of ammonia, stimulates the release of growth hormone from the pituitary gland. Regulates blood sugar levels and reduces lactic acidosis due to muscle load, transfers metabolism to an aerobic pathway. It exhibits nootropic and antiamnesic activity, prevents stressful changes in the metabolism of mediator amino acids, increases the phosphorylation of a number of proteins in the central nervous system. The aspartate component normalizes the processes of nervous regulation.

Arginine and aspartate are rapidly absorbed from the gastrointestinal tract, pass histohematic barriers and are distributed to all organs and tissues. Partially utilized in metabolic processes, the rest is excreted by the kidneys (mainly).

Application of the substance Arginine aspartate

Overwork, general physical and mental fatigue associated with protein deficiency, asthenic conditions in the process of recovery, incl. after infectious diseases and operations, metabolic alkalosis, type I and II hyperammonemia, citrullinemia, argininosuccinic aciduria, and N-acetylglutamate synthetase deficiency.

Contraindications

Hypersensitivity, severe violations of the liver or kidneys, childhood up to 3 years (for solution), up to 12 years (for tablets).

The liver plays a central role in ammonia metabolism. For this reason, patients with chronic diseases hyperammonemia may be observed in the liver. There is evidence that many patients with chronic liver disease have elevated blood ammonia levels in the absence of clinical signs hepatic encephalopathy. Experimental data have been obtained on the stimulating effect of hyperammonemia on liver stellate cells, which may contribute to the progression portal hypertension and fibrosis in the liver. In this regard, it is of interest to use the results of the determination of ammonia in the blood to control the effectiveness various kinds treatment . L-ornithine-L-aspartate (LOLA) is used in the treatment of chronic liver diseases, significantly reduces the level of ammonia in the blood when taken orally. .

The aim of our work was to evaluate the effectiveness of the oral form of LOLA in hyperammonemia in patients with chronic liver diseases at the pre-cirrhotic stage.

Material and research methods

An open clinical study was conducted to evaluate the effectiveness of the LOLA preparation, which included 37 patients (11 men and 26 women, mean age 42.5±6.8 years) with chronic liver diseases (16 with chronic viral hepatitis C, 21 - with fatty liver disease), initially increased level ammonia in the blood minimum degree activity, stage of fibrosis 1-2 (according to elastometry), who were treated in polyclinic No. 3 in Khabarovsk. The anamnesis of the disease ranged from 10 to 25 years.

All patients received LOLA at a dose of 3 g per os 3 times a day for 4 weeks.

The concentration of ammonia ions in the venous blood was determined by the enzymatic method (BIOLABO REAGENTS, France) (norm = 11-35 µmol/l) before and after the course of treatment.

Cognitive function was examined using a number connection test (TST) (normal up to 40 seconds) before and after the course of treatment.

The comparison group consisted of 17 practically healthy volunteers, in whom the level of ammonia in the blood was determined and a number linking test was performed.

Statistical processing of the obtained data was carried out using the Microsoft Office 2010 (Excel) and Biostat-2000 software package. The significance of the difference between the two mean values ​​was assessed by Student's t-test; in the case of repeated measurements, a paired test was used. Differences in the results were considered statistically significant at a significance level p<0,05. Количественные переменные представлены в работе в виде среднего значения ± стандартная ошибка среднего значения (x±mx).

Research results and discussion

The level of ammonia in the blood of 17 practically healthy individuals in the comparison group was 24.0±2.5 µmol/l and was within the normal range. The level of ammonia in the blood of 37 patients included in the study before treatment was increased to 56.1±6.2 µmol/l. Differences in ammonemia between these groups are statistically significant (p1<0,01). Через 4 недели лечения LOLA уровень аммиака в крови у пациентов с гипераммониемий достоверно снизился до 34,7±4,2 мкмоль/л (p2<0,01) (рис.1).

The time to perform SDCT in all 17 practically healthy individuals in the comparison group was less than 40 seconds (35.1 ± 0.4 seconds). The time to perform SDCT in all 37 patients included in the study before treatment exceeded 40 seconds (59.1±0.7 seconds). Differences in the performance time of TSCH between these groups are statistically significant (p1<0,001). Через 4 недели лечения время выполнения ТСЧ у пациентов с гипераммониемией достоверно уменьшилось до 39,2±0,5 сек (p2<0,001) (рис. 2).

Prolongation of SDST time over 40 seconds is usually detected in patients with hepatic encephalopathy.

Thus, we found that hyperammonemia is observed in patients with chronic liver diseases at the pre-cirrhotic stage. Our results confirm the data of other authors. Due to the fact that in all 37 patients with hyperammonemia examined by us, an increase in the time of performing SST over 40 seconds was initially observed, we consider it appropriate to perform SST in patients with chronic liver diseases in the early stages of fibrosis. If it is longer than 40 seconds, it is advisable to study the level of ammonia in the blood. If hyperammonemia is detected, it is necessary to conduct a 4-week course of treatment with the oral form of LOLA, 1.0 g 3 times a day, in order to normalize the level of ammonia in the blood and improve cognitive functions. Hyperammonemia is a leading factor in the development and progression of hepatic encephalopathy, and, perhaps, based on the experimental data obtained by British scientists, a significant factor in the progression of portal hypertension and liver fibrosis. In this regard, the use of hypoammoniemic drugs in chronic liver diseases receives a new additional justification. Further study of the clinical significance of early detection of hyperammonemia and its correction with LOLA is needed.

Execution time of Number Link Test

conclusions

Hyperammonemia occurs in patients with chronic liver diseases at the pre-cirrhotic stage and is accompanied by an increase in the time of performing TST over 40 seconds. Treatment with the oral form of LOLA for 4 weeks reduces the level of ammonia in the blood, improves the performance of the number linking test. Early detection of hyperammonemia and its correction with LOLA is of interest for further research into the possibility of preventing the development and progression of hepatic encephalopathy, portal hypertension, and liver fibrosis.

Bibliography

1. Ong J.P., Aggarwal A., Krieger D., Easley K.A., Karafa M.T., Lente F.V., Arroliga A.C., Mullen K.D. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med 2003; 114:188-93.
2. Jalan R., De Chiara F., Balasubramaniyan V., Andreola F., Khetan V., Malago M., Pinzani M., Mookerjee R.P., Rombouts K. Ammonia produces pathological changes in human hepatic stellate cells and is a target for therapy of portal hypertension. J Hepatol 2016;64: 823-833.
   Vilstrup H., Amodio P., Bajaj J., Cordoba J., Ferenci P., Mullen K., Weissenborn K., Wong P. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American association of the study of liver diseases and the European association for the study of the liver. Hepatology 2014; 60:715-34.
3. Batskov S.S., Sukhonos Yu.A. The effectiveness of the treatment of patients with liver cirrhosis with hepatic encephalopathy with the drug "L-ornithine L-aspartate". Klin persp gastroenterol hepatol 2015; 1:37-41.
   Batskov S.S., Sukhonos Yu.A. Efficacy of L-ornithine-L-aspartate in liver cirrhosis with hepatic encephalopathy. Clin persp gastroenterol gepatol 2015; 1:37-41.
4. Plotnikova E.Yu. The role of L-ornithine-L-aspartate in the complex treatment of patients with hyperammonemia. Klin persp gastroenterol hepatol 2013; 2:1-9.
   Plotnikova Ye.Yu. L-ornithine-L-aspartate in complex treatment of patients with hyperammoniemia. Clin persp gastroenterol gepatol 2013; 2:1-9.
5. Shulpekova Yu.O., Fedosina E.A., Maevskaya M.V., Ivashkin V.T. Experience in the use of the drug "Hepa-Merz" in the treatment of chronic hepatic encephalopathy. Klin persp gastroenterol hepatol 2005; 6:17-23.
   Shulpekova Yu.O., Fedosyina E.A., Mayevskaya M.V., Ivashkin V.T. Application of the drug "Hepa-Merz" in the treatment of chronic hepatic encephalopathy. Clin persp gastroenterol gepatol 2005; 6:17-23.
6. Ong J.P., Oehler G., Kruger-Jansen C., Lambert-Baumann J., Yaunossi Z.V. Oral L-ornithine-L-aspartate improves health-related quality of life in cirrhotic patients with hepatic encephalopathy: an open-label, prospective, multicentre observational study. Clin Drug Invest 2011; 3:213-20.
7. Stauch S., Kircheis G., Adler G., Beckh K., Ditschuneit H., Gortelmeyer R., Hendricks R., Heuser A., ​​Karoff C., Malfertheiner P., Mayer D., Rosch W., Steffens J . Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study. J Hepatol 1998; 28:856-64.
8. Maevskaya M.V., Fedosina E.A. Treatment of complications of liver cirrhosis. Ed. V.T. Ivashkin. Moscow: MEDpress-inform; 2012: 64 p.
   Mayevskaya M.V., Fedosyina E.A. The treatment of complications of cirrhosis. Ivashkin V.T., editor. M.: MEDpress-inform; 2012: 64p.
9. Bogomolov P.O., Bueverov A.O., Uvarova O.V., Matsievich M.V. Hyperammonemia in patients with pre-cirrhotic liver disease: is it possible? Klin persp gastroenterol hepatol 2013; 5:3-8.
   Bogomolov P.O., BuyeverovA.O., Uvarova O.V., Matsievich M.V. Hyperaamoniemia in Liver disease at precirrhotic stage: is it possible? (Preliminary data of "SMART RADAR" study). Clin persp gastroenterol gepatol 2013; 5:3-8.
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Summary

Purpose of the study. Evaluation of the effectiveness of the oral form of LOLA in hyperammonemia in patients with chronic liver diseases at the pre-cirrhotic stage.

Material and methods. An open clinical study was conducted to evaluate the effectiveness of LOLA in the treatment of 37 patients with hyperammonemia in chronic liver disease, stage 1-2 fibrosis.

Results. There was a positive effect of treatment on the level of ammonia in the blood and the time to perform the number linking test. Ammonia levels decreased from 56.1 ± 6.2 µmol/L after 4 weeks of LOLA treatment to 34.7 ± 4.2 µmol/L (p<0,01), время выполнения ТСЧ — с 59,1 ± 0,7 сек до 39,2 ± 0,5 сек (p<0,001).

Conclusions. Hyperammonemia occurs in patients with chronic liver diseases at the pre-cirrhotic stage and is accompanied by an increase in the time of performing TST over 40 seconds. Treatment with the oral form of LOLA for 4 weeks reduces the level of ammonia in the blood, improves the performance of the number linking test. Early detection of hyperammonemia and its correction with LOLA is of interest for further research into the possibility of preventing the development and progression of hepatic encephalopathy, portal hypertension, and liver fibrosis.

E.A. Ageeva 1,gastroenterologist of the highest qualification category, KGBUZ "City Clinical Polyclinic No. 3" of the Ministry of Health of the Khabarovsk Territory,[email protected]
S.A. Alekseenko 2,Doctor of Medical Sciences, Professor, Head of the Department of Hospital Therapy, Far Eastern State Medical University, Ministry of Health of Russia,[email protected] _dv.ru

1 KGBUZ "City clinical polyclinic No. 3" ("City clinical polyclinic No. 3"), Ministry of Health of the Khabarovsk Territory
2 SBEE HPE "Far Eastern State Medical University"(“Far Eastern State Medical University”) of the Russian Ministry of Health

1 kg - polyethylene bags (1) double - fiber drums.
5 kg - polyethylene bags (1) double - fiber drums.
10 kg - polyethylene bags (1) double - fiber drums.
15 kg - polyethylene bags (1) double - fiber drums.
25 kg - polyethylene bags (1) double - fiber drums.

Description of the active ingredients of the drug Ornithine»

pharmachologic effect

Hypoammoniemic agent. Reduces elevated levels of ammonia in the body, in particular in liver diseases. The action is associated with participation in the ornithine cycle of Krebs urea formation (formation of urea from ammonia). Promotes the production of insulin and growth hormone. Improves protein metabolism in diseases requiring parenteral nutrition.

Ornithine aspartate in the body dissociates into the amino acids ornithine and aspartate, which are absorbed in the small intestine by active transport through the intestinal epithelium. Excreted with urine.

Indications

Acute and chronic liver diseases accompanied by hyperammonemia. Hepatic encephalopathy.

For dynamic study of pituitary function.

As a corrective additive to preparations for parenteral nutrition in patients with protein deficiency.

Dosing regimen

For oral administration - 3-6 g 3 times / day after meals. V / m - 2-6 g / day; IV bolus 2-10 g/day; the frequency of administration - 1-2 times / day. In / in drip 10-50 g / day. The duration of infusion, frequency and duration of treatment are determined individually.

Side effect

Seldom: skin manifestations.

In some cases: nausea, vomiting.

Contraindications

Severe renal dysfunction (serum creatinine more than 3 mg / 100 ml).

Pregnancy and lactation

During pregnancy, the use is possible only under the strict supervision of a physician.

If necessary, use during lactation should decide on the termination of breastfeeding.

Application for violations of kidney function

Contraindicated in severe renal dysfunction (serum creatinine more than 3 mg/100 ml).

special instructions

If nausea or vomiting occurs, the rate of administration should be optimized.

When using a particular dosage form of ornithine, compliance with specific indications should be observed.

Influence on the ability to drive vehicles and control mechanisms

Ornithine can cause disturbances in concentration and speed of psychomotor reactions.