Heptral

Heptral is a hepatoprotective medication that also has an antidepressant effect.

It demonstrates cholekinetic and choleretic activity, and in addition has a regenerating, antifibrinolytic, detoxifying, neuroprotective and antioxidant effect. The medicine allows not only to replenish the deficiency of ademetionine in the body, but also stimulates the production of this element in various organs (primarily this concerns the spinal cord with the brain, as well as the liver).

Indications Heptral

It is used for the following disorders:

• intrahepatic cholestasis;
• liver pathologies, including cholangitis and non-calculous cholecystitis in the chronic stage;
• precirrhotic as well as cirrhotic conditions;
• liver intoxications of alcoholic, viral or medicinal (antiviral or anti-tuberculosis agents, antibiotics, contraception and chemotherapy drugs) origin;
• chronic hepatitis or fatty liver disease;
• state of depression;
• abstinence (also of alcoholic origin).

Release form

The therapeutic substance is released in tablets - 10 or 20 pieces per pack.

In addition, it is produced as an injection lyophilisate - inside 5 ml vials. The box contains 5 such vials and a solvent.

Pharmacodynamics

Ademetionine is a component observed in almost all physiological fluids along with body tissues. The chemical structure of the drug makes it a donor of the methyl subcategory in transmethylation processes. The substance is the basis of many biochemical thiol bonds (taurine with cysteine, coenzyme A, etc.) in the development of transsulfuration, and in addition, a polyamine precursor (spermidine and putrescine with spermine, which are part of the ribosomal structure). It also stimulates cellular restoration.

Transmethylation by ademetionine on various components within the body (neurotransmitters, hormones, phospholipids and proteins) is a very important metabolic process. [ 1 ]

Long-term use of the drug causes an increase in liver glutamine levels, as well as plasma taurine and cysteine; in addition, the amount of serum methionine decreases, from which one can draw a conclusion regarding the stabilization of intrahepatic metabolic processes and improvement of liver function. [ 2 ]

The drug has a choleretic effect through stimulation of phosphatidylcholine binding inside hepatocyte membranes, as well as polarization and increase in their elasticity. As a result, the transport activity of bile acids improves, which allows them to be excreted into the biliary system. In addition, the drug helps to rid bile acids of toxicity - in the process of their sulfation. This improves their renal elimination and simplifies their passage through the hepatocyte walls and excretion with bile.

The use of Heptral leads to the development of positive dynamics of direct bilirubin values, as well as the activity of aminotransferases and alkaline phosphatase. The hepatoprotective and choleretic properties of the drug continue to be preserved for a period of 3 months from the moment of drug withdrawal.

The level of ademetionine in a child or teenager is much higher than in an elderly person, because its values decrease with age. At the same time, the values of ademetionine are lower in people with depression. At high levels of the substance, the processes of exchange of catecholamines (norepinephrine with adrenaline), histamine and indolamines (melatonin with serotonin) are stimulated inside the brain tissue.

The use of the drug stabilizes phospholipid methylation inside the walls of neuronal cells, normalizing the movement of neuronal impulses and increasing the period of activity of nerve cells.

Experiments have established the effectiveness of Heptral in the treatment of depression. Its antidepressant effect develops at a high rate, reaching peak values by the 5th-7th day of drug use. During drug use, ademetionine undergoes transformation phases similar to the endogenous component.

Pharmacokinetics

Suction.

When using the drug, the pharmacokinetics of ademetionine has a biexponential nature with a stage of pronounced and high-speed tissue distribution, as well as with a final stage of elimination with a half-life of approximately 90 minutes.

The absorption of the drug after administration is almost complete (96%), and the Cmax values are recorded after 45 minutes. When taking an ademetionine tablet orally, its Cmax values are tied to the portion size and are equal to 0.5-1 mg/l; it takes 3-5 hours to achieve this value when administering a single portion in the range of 0.4-1 g. The intraplasmic level decreases to the initial marks over a period of 24 hours.

The values of bioavailability when taken orally increase when the drug is taken between meals. After oral administration, the tablets are absorbed in the gastrointestinal tract and significantly increase the values of plasma ademetionine.

Animal testing using isotope processes has confirmed that oral administration of ademetionine stimulates the formation of methylated intrahepatic ligaments. In addition, it has been shown that the substance is absorbed through the typical metabolic pathways that are characteristic of endogenous ligaments (transsulfuration with transmethylation, decarboxylation, etc.).

Distribution processes.

The distribution volume values are 0.41 and 0.44 l/kg for portions of 0.1 and 0.5 g. Protein synthesis is quite weak – equal to ≤5%.

Exchange processes.

The processes by which ademetionine is produced, regenerated and assimilated are called the ademetionine cycle. During the first phase of this cycle, ademetionine-dependent methylase uses ademetionine as a substrate for the production of S-adenosyl-homocysteine, and this element is then hydrolyzed to form adenosine with homocysteine (with the participation of S-adenosyl-homocysteine hydrolase).

In this process, homocysteine is converted back into methionine – through the transfer of the methyl subcategory from 5-methyltetrahydrofolate. Finally, methionine is transformed into ademetionine, which completes the cycle.

Excretion.

In radioisotope tests involving volunteers, oral administration of radiolabeled (methyl 14C type) ademetionine demonstrated excretion of the radioactive element in the urine, amounting to 15.5±1.5% after 48 hours; 23.5±3.5% was excreted in the feces after 72 hours. At the same time, approximately 60% of the drug remained incorporated within stable pools.

Dosing and administration

The drug is taken orally (in tablets) or administered intravenously/intramuscularly (lyophilisate dissolved in the supplied L-lysine solvent before the injection procedure). The intravenous procedure is performed at a very low speed.

During intensive therapy, Heptral is administered by injection (the daily dose is 1-2 vials (0.4-0.8 g) for the first 14-21 days of treatment).

For maintenance treatment, the medication is taken orally in a daily dosage of 800-1600 mg (equivalent to 2-4 tablets).

The medicine should be taken between meals. It is recommended to do this during the first half of the day, because when the medicine is administered, a slight nervous excitement may be observed. The tablets are swallowed without chewing and washed down with plain water.

The duration of the maintenance treatment cycle is selected by the attending physician (on average it is 0.5-2 months).

• Application for children

There is no information regarding the medicinal efficacy and safety of its use in pediatrics.

Use Heptral during pregnancy

The drug should not be prescribed in the 1st and 2nd trimesters; in the 3rd trimester, its use is possible, but only in situations where the probable benefit is more expected than the possible risks of complications.

If the use of Heptral is required during breastfeeding, the issue of stopping breastfeeding must first be resolved.

Contraindications

Contraindicated for use by people with personal intolerance to the components of the medication.

Side effects Heptral

Main side effects:

• disorders associated with the gastrointestinal tract: dyspepsia, nausea, heartburn or gastralgia;
• problems with the functioning of the central nervous system: the sleep rhythm may change (to correct it, you can take sedatives at night);
• allergy symptoms.

Interactions with other drugs

There is information regarding the occurrence of serotonin intoxication in people who used ademetionine together with clomipramine. Therefore, although the possibility of interaction is only theoretical, it is necessary to use the drug very carefully in combination with SSRI substances, herbal elements that contain tryptophan, as well as with tricyclics (including clomipramine).

Storage conditions

Heptral must be stored in a place protected from moisture penetration, at temperatures within the 25°C mark.

Shelf life

Heptral can be used for a period of 36 months from the date of manufacture of the medicinal element.

Analogues

Analogues of the drug are the drugs Heptor and Ademetionine.

Reviews

Many patients call Geptral one of the most effective or even the only really helpful hepatoprotective medicine. Many reviews indicate that the drug helps very well in treating the liver. Although there are also opinions of those who did not like the drug at all. Among the disadvantages, they mainly note the very high cost of the drug.