PEGylated interferons are synthesized from conventional ones by modifying them. The resulting product has improved characteristics that are used in the treatment of viral diseases (mainly hepatitis). There are 2 main varieties of such drugs. Most often they are used together with Ribavirin and an NS3/4A protease inhibitor.
Destination
PEGylated interferons are antiviral drugs that affect the human immune system. Their other names are peginterferons, peg-INF. The prefix "peg" comes from an abbreviated version of "polyethylene glycol". Its molecules are introduced into the composition of conventional interferon in order to increase the duration of the effect of the active substance in the body.
Pegylated interferons have the following advantages over their standard versions:
- highly effective (clinically proven);
- possibility of reducing the number of injections(due to extended half-life);
- higher stability of the active substance;
- fewer side effects (allergic reactions and unwanted immunogenicity processes).
The pegylation technology was first described in 1977. Prior to this, it was believed that proteins can only be integrated into the structure of low molecular weight compounds. At the same time, the high molecular weight of modified interferons causes the main disadvantage of these drugs - difficult excretion from the body. Excretion occurs mainly through the kidneys and with feces.
Polydispersity (a combination of molecules that differ in the amount and localization of polyethylene glycol attachment) and a large volume of distribution in the body impair the filtration of the substance through the kidneys. In this regard, a promising direction in the technology of these drugs is the improvement of the pegylation process. The history of the use of modified interferons in medicine has about 10 years.
Views
The following drugs of this group are used in therapeutic practice:
- 2 types of alpha modification (pegylated interferon alpha-2a and 2b). Means made on their basis are characterized by a different chemical structure. There are no fundamental differences between them. Pegylated interferon alpha has a higher molecular weight (about 40 kDa) than the second type. Therefore, it is characterized by a more prolonged action.
- Beta peg-INF. Manufacturedpegylated interferon beta drugs are a new generation of drugs. They are used to treat multiple sclerosis. This substance is obtained using the biotechnology of recombinant proteins grown in cell culture, which are isolated from the ovaries of hamsters. The exact mechanism of the effect of the active substance is unknown. It involves the stimulation of anti-inflammatory and suppression of pro-inflammatory polypeptide messenger molecules.
According to the latest medical research, the best antiviral efficacy is shown by the combined administration of both alpha-interferons, as well as the simultaneous administration of the drug "Ribavirin".
Forms of release and storage conditions
Pegylated interferons alpha 2b and 2a are sold on the Russian pharmaceutical market as part of 4 drugs:
- "Pegasis" (manufactured by Roche, Switzerland). Solution for subcutaneous administration, clear or light yellow. It is produced in finished form in syringes-tubes of 180 (135) mcg. The package contains 1 or 4 syringes.
- "Pegintron" (pharmaceutical corporation Schering-Plough, USA). It is produced in the form of a two-chamber syringe pen, in one compartment there is a dry lyophilisate, in the second - a solvent.
- "PegAltevir" ("BioProcess", Russia). The package contains 2 bottles - one with the active substance in the form of a white powder, the second with a solvent.
- "Algeron" (manufactured by the international innovation company "Biocad"). Colorless or yellowish solution. The package contains 1 or 4 syringes.
All drugsshould be stored and transported in a dark place at an ambient temperature of +2 … +8 °C. The shelf life of the first three drugs from the above list is 3 years, the last one is 2 years.
Properties
The main properties of pegylated interferons are as follows:
- suppression of the vital activity and reproduction of viruses occurs due to the influence on the mechanism of transcription of their genes;
- the active substance is detected in human blood after 3-6 hours, and its maximum level is reached on the 3rd-4th day;
- slower increase in blood concentration as a result of sustained release of the drug;
- active substance accumulates mainly in the blood and in functionally active liver cells;
- half-life is 80 and 160 hours, respectively, for intravenous and subcutaneous injection (with standard interferon - 4 hours);
- peginterferon-alpha 2b molecules are smaller, so they more actively penetrate into the peripheral blood, lymph nodes, kidneys and other organs;
- Excretion is mainly through the kidneys.
Due to the increased half-life of these substances in the human body, the number of necessary injections per week is reduced - from 3 (for standard interferon) to 1 (for pegylated modification). At the same time, a large number of bound molecules reduces the biological activity of the product. So, in peg-INF alpha 2b, it is at the level of 37% of the standard non-pegylated interferon, andmodification alpha 2a has 7%.
Composition
The composition of drugs based on peg-interferons is shown in the table below.
| Drug name | Active substance | Additional components |
| Pegasis | Peginterferon alfa-2a | Ascorbic acid, acetic acid, sodium chloride, solvent - water, phenylcarbinol, sodium acetate, polysorbate-80 emulsifier |
| Algeron | Peginterferon alfa-2b | Sodium acetate trihydrate, acetic acid, disodium edetate, sodium chloride, polysorbate-80, water |
| PegAltevir, Pegintron | Peginterferon alfa-2b | Sodium Phosphate, Sucrose, Polysorbate-80, Water |
Pegylated interferons: indications
Peginterferons alfa are recommended in the treatment of hepatitis:
- type B - with positive and negative hepatitis B anti-HBe antigen, with an increased level of the enzyme alanine aminotransferase in the blood, with inflammation, fibrosis and other liver lesions;
- type C - for patients with or without cirrhosis, HIV-infected.
Drugs can be used both in monotherapy and in combination with each other and other antiviral agents.
Application Features
Treatment with pegylated interferons is characterized by the following features:
- "Pegasis" - an injection is injected into the thigh or abdomen 1 time in 7 days. Duration of therapy - 48 weeks.
- "Algeron", "PegAltevir" - subcutaneous injection into the thigh or abdominal wall. The injection site must be changed. The injection is done once a week, it is recommended to administer the injection at bedtime. The duration of treatment is the same as for the previous remedy. In the absence of an early virological effect (EVR) after 12 weeks or the detection of viral RNA after 24 weeks, therapy is stopped. Each virus genotype has its own typical treatment regimen.
- "Pegintron" - injected subcutaneously, duration of therapy - 24-52 weeks and 6 months for hepatitis B and C, respectively. To reduce pain, the injection site is changed. If, after a course of RNA treatment, the virus is still detected, then the therapy is extended for another six months. When the pathogen is detected again, it is stopped.
The dosage of drugs is observed according to the instructions. Its calculation is based on the weight of the patient and the treatment regimen - double (with Ribavirin), triple (with Ribavirin and an NS3 / 4A protease inhibitor) or monotherapy. Ribavirin is taken daily with food. Medicines are used only as prescribed by a doctor and under his supervision.
Contraindications
Pegylated interferon therapy is not available in the following conditions:
- pregnancy and lactation (since there are no studies on the excretion of active substances in milk and their effect on the fetus);
- hypersensitivity to drug components;
- decompensated cirrhosis of the liver;
- autoimmune hepatitis;
- diabetes mellitus in the stage of decompensation;
- age up to 18 years (for triple and monotherapy) and up to 3 years (for dual therapy);
- pathology of the thyroid gland (deficiency and excess of its hormones).
With caution, these drugs are prescribed to those patients who have mental disorders, diseases of the kidneys, cardiovascular system, autoimmune pathologies and when taking drugs with a myelotoxic effect (suppressing the hematopoietic function of the bone marrow).
Side effects
The most common side effects (in 20-30% of patients) with these drugs are:
- general weakness;
- increased body temperature;
- headache;
- sleep disorders;
- irritability;
- depression.
In 10-14% of patients, drugs are not used due to their intolerance.
Other possible side effects include the following:
- neutropenia (a life-threatening condition in which the number of neutrophils in the blood decreases);
- nausea, vomiting;
- diarrhea;
- joint and muscle pain;
- skin itching;
- hair loss;
- increaseblood pressure;
- tachycardia;
- stunting and development in children and adolescents;
- severe mental disorders (suicidal thoughts, mania, bipolar disorder and others).
