Vilerm Mechanism of Action

Pharmacology: Pharmacodynamics: Tablet: Acyclovir is a synthetic purine nucleoside analogue antiviral agent with in vitro and in vivo inhibitory activity against herpes simplex virus (HSV) types I and II, varicella zoster virus, Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Acyclovir has the greatest antiviral activity against HSV type I followed (in decreasing order of potency) by HSV type II, VZV, EBV and CMV. Acyclovir exerts its antiviral effect by interfering with DNA synthesis and inhibiting viral replication. The antiviral activity of Acyclovir appears to depend principally on the intracellular conversion of the drug to Acyclovir triphosphate. In cells infected with herpesvirus in vitro, Acyclovir is converted to Acyclovir monophosphate principally via virus-coded thymidine kinase (TK); the monophosphate is phosphorylated to the diphosphate via cellular guanylate kinase and then to the triphosphate via other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA. These causes termination of the growing viral DNA chain and inactivation of the viral DNA polymerase.
Powder for infusion: Acyclovir is a synthetic purine nucleoside analogue with in vitro inhibitory activity against herpes simplex virus (HSV) types 1 and 2, varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Acyclovir has the greatest antiviral activity against HSV-1, followed (in decreasing order of potency) by HSV-2, VZV, EBV and CMV. The inhibitory activity of Acyclovir for these viruses is highly selective. The enzyme thymidine kinase (TK) of normal, non-infected cells does not use Acyclovir effectively as a substrate, hence toxicity to mammalian host cells is low; however, TK encoded by HSV, VZV and EBV converts Acyclovir to Acyclovir monophosphate, a nucleoside analogue, which is further converted to the diphosphate and finally to the triphosphate by cellular enzymes. Acyclovir triphosphate interferes with the viral DNA polymerase and inhibits viral DNA replication with resultant chain termination following Acyclovir triphosphate incorporation into the viral DNA.
Pharmacokinetics: Tablet: Absorption of Acyclovir from gastrointestinal tract is incomplete. Plasma Acyclovir concentrations were not dose proportional over the oral dosing. Bioavailability of oral Acyclovir is about 10 to 20%. Food does not appear to affect absorption of Acyclovir. Peak plasma concentrations of Acyclovir usually occur within 1.5-2.5 hours after oral administration. Acyclovir is widely distributed into body tissues and fluids including the brain, kidney, saliva, lung, liver, muscle, spleen, uterus, vaginal mucosa and secretions, CSF and herpetic vesicular fluid. Acyclovir is approximately 9-33% bound to plasma proteins. Acyclovir crosses the placenta and is distributed into breast milk. Acyclovir is metabolized partially to 9-carboxymethoxymethylguanine and minimally to 8-hydroxy-9-(2-hydroxyethoxymethyl)guanine. Acyclovir is excreted largely unchanged in the urine. Fecal excretion may account for about 2% of a dose. Acyclovir is removed by hemodialysis.
Powder for infusion: When Acyclovir was administered by intravenous infusion, Acyclovir is widely distributed into body tissues and fluids in the body including the brain, kidney, saliva, lung, liver, muscle, spleen, uterus, vaginal mucosa and secretions, cerebrospinal fluid (CSF) and herpetic vesicular fluid. Following IV infusion, Acyclovir generally diffuses well into CSF. In patients with uninflamed meninges, CSF concentrations of Acyclovir are reported to be approximately 50% of concurrent serum Acyclovir concentrations. Plasma protein binding is relatively low (9 to 33%). Acyclovir crosses the placenta and is distributed in breast milk. Acyclovir is metabolized partially to 9-carboxymethoxymethylguanine and minimally to 8-hydroxy-9-(2-hydroxyethoxymethyl)guanine. Acyclovir is excreted largely unchanged in the urine and Acyclovir is excreted through feces.
Acyclovir is removed by hemodialysis.