Zoylex Mechanism of Action



Korea United Pharm


S Charoen Bhaesaj Trading
Full Prescribing Info
Pharmacology: Pharmacodynamics: Aciclovir, a synthetic acyclic purine nucleoside analog, is a substrate with a high degree of specificity for herpes simplex and varicella-zoster-specified thymidine kinase. Aciclovir is a poor substrate for host cell-specified thymidine kinase. Herpes simplex and varicella-zoster-specified thymidine kinase transform aciclovir to aciclovir monophosphate which is then transformed by number of cellular enzymes to aciclovir diphosphate and aciclovir triphosphate. Aciclovir triphosphate is both an inhibitor of, and a substrate for, herpes virus-specified DNA polymerase. Although the cellular α-DNA polymerase in infected cells may also be inhibited by aciclovir triphosphate, this occurs only at concentrations of aciclovir triphosphate which are higher than those which inhibit the herpes virus-specified DNA polymerase. Aciclovir is selectively converted to its active form in herpes virus-infected cells and is thus preferentially taken up by these cells. Aciclovir has demonstrated a very much lower toxic potential in vitro for normal uninfected cells because: less is taken up; less is converted to the active form; cellular α-DNA polymerase has a lower sensitivity to the action of the active form of the drug. A combination of the thymidine kinase specificity, inhibition of DNA polymerase and premature termination of DNA synthesis results in inhibition of herpes virus replication. No effect on latent non-replicating virus has been demonstrated. Inhibition of the virus reduces the period of viral shedding, limits the degree of spread and level of pathology, and thereby facilitates healing. During suppression, there is no evidence that aciclovir prevents neural migration of the virus. It aborts episodes of recurrent herpes due to inhibition of viral replication following reactivation.
Pharmacokinetics: Absorption: In adults with normal renal function receiving single aciclovir doses ranging from 0.5 to 15 mg/kg or multiple doses ranging from 2.5 to 15 mg/kg every 8 hours indicate that plasma concentrations of the drug are dose proportional.
Distribution: Aciclovir 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. CSF aciclovir concentration is 50% of plasma concentrations.
The apparent volume of distribution of aciclovir is reported to be 32.4-61.8 L/1.73 m2 in adults and 28.8, 31.6, 42.0, or 51.2-53.6 L/1.73 m2 in neonates up to 3 months of age, children 1-2 years, 2-7 years, or 7-12 years of age, respectively. Aciclovir is approximately 9-33% bound to plasma proteins.
Metabolism: Converted by viral enzymes to aciclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes.
Excretion: Renal excretion of unchanged drug by glomerular filtration and tubular secretion is the major route of aciclovir elimination, accounting for 62 to 91% of the dose administered.
The half-life elimination (terminal phase) of aciclovir is reported to be 3.8 ± 1.19 hours in neonate and infants ≤3 months, 2.36 ± 0.97 hours in infants >3 months to children ≤12 years, ~2.5 hours in adults with normal renal function, 20 hours in adults with ESRD, and ~5 hours in patients with hemodialysis.
The pharmacokinetics of aciclovir in children generally are similar to that reported in adults.
Aciclovir plasma concentrations are higher in geriatric patients than in younger adults, in part due to age-related changes in renal function.
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