Sign Out
Pharmacology: Pharmacodynamics: Aciclovir is a synthetic purine nucleotide analogue with in vitro and in vivo inhibitory activity against human herpes viruses, including herpes simplex virus (HSV) types I and II and varicella zoster virus (VZV). The inhibitory activity of Aciclovir for HSV I and HSV II and VZV is highly selective. The enzyme thymidine kinase (TK) of normal, uninfected cells does not use Aciclovir effectively as a substrate, hence toxicity to mammalian host cells is low; however, TK encoded by HCV and VZV converts Aciclovir to Aciclovir monophosphate, a nucleoside analogue which is further converted to the diphosphate and finally to the triphosphate by cellular enzymes. Aciclovir triphosphate interferes with the viral DNA polymerase and inhibits viral DNA replication with resultant chain termination following its incorporation into the viral DNA.
Prolonged or repeated courses of Aciclovir in severely immune-compromised individuals may result in the selection of virus strains with reduced sensitivity, which may not respond to continued Aciclovir treatment. Most of the clinical isolates with reduced sensitivity have been relatively deficient in viral TK, however, strains with altered viral TK or viral DNA polymerase have also been reported. In vitro exposure of HSV isolates to Aciclovir can also lead to the emergence of less sensitive strains. The relationship between the in-vitro determined sensitivity of HSV isolates and clinical response to Aciclovir therapy is not clear.
Pharmacokinetics: About 15 to 30% of a dose of Aciclovir given by mouth is considered to be absorbed from the gastrointestinal tract. A dose of 200 mg Aciclovir every 4 hours by mouth is reported to produce maximum and minimum steady-state plasma concentrations of 0.7 and 0.4 mcg per mL respectively; equivalent values following 400 mg doses are 1.2 and 0.6 mcg per mL. Aciclovir crosses the placenta and is excreted in breast milk in concentrations approximately 3 times higher than those in maternal serum.
