pharmachologic effect
Virostatic preparation containing active ingredient acyclovir. Acyclovir is a synthetic substance, close in structure to guanine (a constituent part of nucleic acids, is complementary to cytosine), when interacting with specific enzymes, acyclovir is converted into a pharmacologically active substance. In cells infected with viruses, a specific enzyme, thymidine kinase, is produced, which, through several chemical reactions, converts acyclovir into acyclovir triphosphate. Due to saturation of the cytoplasm of the infected cell with acyclovir triphosphate, replication of DNA of viruses occurs, which leads to disruption of normal virus multiplication and the formation of nonviable viral units. The mechanism of action of the drug is based on its structural similarity with deoxyguanosine triphosphate, due to which there is a competitive replacement of the nucleotide with acyclovir triphosphate during the synthesis of viral DNA. The drug does not affect healthy cells of the body, because they lack the enzyme thymidine kinase and acyclovir remains inactive form. In addition, the concentrations of acyclovir in infected cells are significantly higher than in healthy cells. The drug exhibits virostatic activity with respect to herpes simplex virus type I and II, a virus that causes varicella. Acyclovir is moderately active against cytomegaloviruses.
With prolonged use of the drug, especially in patients with immunodeficiency, the development of resistance of viruses to drugs containing acyclovir was observed. Resistant strains of viruses are characterized by a low content or disorder of the thymidine kinase structure, changes in the structure of the viral DNA polymerase.
When the drug is used in the form of an ophthalmic ointment, acyclovir is rapidly absorbed through the cornea and creates high concentrations in the intraocular fluid. Systemic absorption of the drug when applied to the cornea is not significant, acyclovir is practically not detected in the blood plasma, some amount of acyclovir is determined in the urine.
When using the preparation in the form of an ointment, the systemic absorption of acyclovir is negligible.
With intravenous infusion of the drug, the maximum concentration in the blood plasma was noted 1 hour after the infusion. The half-life in adults is 2.9 hours, in newborns 3.8 hours.
After oral administration of the drug, the active substance is partially absorbed into the total blood flow. When taking the drug at a dose of 200 mg every 4 hours, the maximum equilibrium concentration of the drug in the blood plasma is about 3.1 μmol, and the minimum equilibrium concentration of the drug is about 1.8.
The degree of connection with plasma proteins is low (from 9 to 33%). The drug in high concentrations is determined in the cerebrospinal fluid. Acyclovir is partially metabolized in the liver. It is excreted mostly by the kidneys, both in unchanged form and in the form of metabolites.
In elderly people, the half-life of acyclovir increases somewhat.
In patients with renal failure, the half-life of acyclovir is up to 19.5 hours, while hemodialysis, the half-life is reduced to 5.7 hours.
Indications for use
The drug is intended for local and systemic use in patients with such diseases:
- infectious diseases of the skin and mucous membranes caused by the herpes virus type I and II, including for the therapy of primary genital herpes and its relapses;
- Infectious diseases caused by the virus of chicken pox and herpes zoster;
- Type I and II herpetic infection in newborns;
- the drug is also used to prevent infectious diseases caused by the herpes simplex virus in patients with immunodeficiency;
- for the prevention of cytomegalovirus infection in bone marrow transplantation operations.
