Laciclovir is a synthetic nucleoside analogue active against herpesviruses. Acyclovir tablets are formulations of an antiviral drug for oral administration.
Each 800 mg aciclovir tablet contains 800 mg aciclovir and the inactive ingredients corn starch, microcrystalline cellulose, magnesium stearate and sodium starch glycolate.
Each 400 mg acyclovir tablet contains 400 mg acyclovir and the inactive ingredients corn starch, microcrystalline cellulose, magnesium stearate and sodium starch glycolate.
Laciclovir is a white crystalline powder with the molecular formula C 8H 11N 5O 3 and a molecular weight of 225. The maximum solubility in water at 37 ° C is 2.5 mg / ml. The pkas of acyclovir are 2.27 and 9.25.
The chemical name of acyclovir is 6 H-purin-6-one, 2-amino-1,9-dihydro-9 [(2-hydroxyethoxy) methyl], it has the following structural formula:
Antiviral mechanism of action
Laciclovir is a synthetic purine nucleoside analog with in vitro and in vivo inhibitory activity against herpes simplex virus type 1 (HSV-1), 2 (HSV-2) and varicella-zoster virus (VZV). The inhibitory activity of cyclovir is highly selective due to its affinity for the thymidine kinase (TK) enzyme encoded by HSV and VZV. This viral enzyme converts laciclovir to aciclovir monophosphate, a nucleotide analogue. Monophosphate is further converted to diphosphate by cellular guanylate kinase and to triphosphate by a number of cellular enzymes. In vitro, laciclovir triphosphate prevents replication of the herpes viral DNA. This is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation and termination of the growing viral DNA chain, and 3) inactivation of viral DNA polymerase.The greater antiviral activity of acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by viral TK.
The quantitative relationship between the in vitro susceptibility of herpes viruses to antivirals and the clinical response to therapy has not been established in humans and virus susceptibility testing has not been standardized. The results of the susceptibility tests, expressed as the drug concentration required to inhibit the growth of the virus in cell culture by 50% (IC 50), vary greatly depending on a number of factors. Using plaque reduction assays, the IC50 against herpes simplex virus isolates ranges from 0.02 to 13.5 mcg / mL for HSV-1 and from 0.01 to 9.9 mcg / mL for HSV-2. LIC 50 for laciclovir compared to most laboratory strains and clinical isolates of VZV ranges from 0.12 to 10.8 mcg / mL. Laciclovir also demonstrates activity against the Oka vaccine strain of VZV with a mean IC 50 of 1.35 mcg / mL.
Resistance of HSV and VZV to allaciclovir can result from qualitative and quantitative changes in viral TK and / or DNA polymerase. Clinical isolates of HSV and VZV with reduced susceptibility to aciclovir were recovered from immunocompromised patients, particularly with advanced HIV infection. While most acyclovir-resistant mutants isolated so far from immunocompromised patients have been found to be TK-deficient mutants, other mutants involving the viral TK gene (partial TK and altered TK) and DNA polymerase have been isolated. TK-negative mutants can cause severe disease in immunocompromised infants and adults. The possibility of viral resistance to allaciclovir should be considered in patients who show poor clinical response during therapy.