Pharmacology: Pharmacodynamics: Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against Herpes simplex virus types 1 (HSV-1), 2 (HSV-2) and Varicella-zoster virus (VZV).
The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, acyclovir triphosphate stops replication of herpes viral DNA. This is accomplished in 3 ways: Competitive inhibition of viral DNA polymerase.
Incorporation into and termination of the growing viral DNA chain.
Inactivation of the viral DNA polymerase.
The greater antiviral activity of acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the viral TK.
Pharmacokinetics: Systemic absorption of topical acyclovir is minimal and the resulting blood levels are below the limit of detection. It is therefore impossible to characterize the kinetics of bioavailability of topical acyclovir. Toxic effects are unlikely with topical acyclovir because the drug does not reach the systemic circulation.