Zevin Mechanism of Action

Pharmacology: Pharmacodynamics: Aciclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus type 1 (HSV-1), 2 (HSV-2) and varicella zoster virus (VZV). In cell culture, aciclovir's highest antiviral activity is against HSV-1, followed in decreasing order of potency against HSV-2 and VZV.
The inhibitory activity of aciclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts aciclovir into aciclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. The formation of aciclovir monophosphate appears to be the rate-limiting step in the formation of aciclovir triphosphate.
Aciclovir also is apparently converted to aciclovir triphosphate by other mechanisms since the drug has some activity against several viruses that apparently do not code for viral TK.
In vitro, aciclovir 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; and inactivation of the viral DNA polymerase.
Pharmacokinetics: Absorption: Aciclovir is only partially absorbed from the gut. The average oral bioavailability varies between 10% and 20% (bioavailability decrease with increased dose). Mean peak plasma concentration shown as follows: Css_max: at 200 mg is 0.83 mcg/ml; at 400 mg is 1.21 mcg/ml; at 800 mg is 1.61 mcg/ml.
Css_trough: at 200 mg is 0.46 mcg/ml; at 400 mg is 0.63 mcg/ml; at 800 mg is 0.83 mcg/ml.
Poorly absorbed, absorption improves with multiple small doses compared to one large daily dose.
Distribution: Plasma protein binding of aciclovir is relatively low between 9% to 33%. Cerebrospinal fluid concentration is approximately 50% of corresponding plasma concentration at steady-state.
V_dss: Neonates to 3 months of age: 28.8 L/1.73 m².
Children 1 to 2 years: 31.6 L/1.73 m².
Children 2 to 7 years: 42 L/1.73 m².
Adult: 0.8 L/kg.
Metabolism: Aciclovir is converted by viral enzymes to aciclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes. The only significant urinary metabolite is 9-[(carboxymethoxy)methylguanine].
Excretion: Excrete as unchanged and metabolite form in urine between 62% to 91%. Plasma elimination half-life is 2.5 to 3.3 hours.
Special patient populations: Renal function impairment: The half-life and total body clearance of aciclovir are dependent on renal function. A dosage adjustment is recommended for patients with reduced renal function.
Elderly: Aciclovir plasma concentrations are higher in elderly patients compared with younger adults, in part due to age-related changes in renal function. Dosage reduction may be required in elderly patients with underlying renal impairment.