Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.
Active Ingredient / Synonyms
Aciclovir | Aciclovirum | Acycloguanosine | Acyclovir |
A guanosine analog antiviral drug that acts as an antimetabolite. Aciclovir is used for the treatment of herpes simplex virus infections, varicella zoster (chickenpox) and herpes zoster (shingles). Aciclovir has also been investigated for the treatment of herpes labialis applied using an iontophoretic device. Currently approved drugs for the treatment of herpes labialis (cold sores) exhibit low levels of efficacy due to the limited ability of the drugs to penetrate the skin to the site where the herpes virus is replicating. Iontophoresis uses electric current to enhance the delivery of drugs through the skin.
For the treatment and management of herpes zoster (shingles), genital herpes, and chickenpox.
Mechanism of Action
Viral (HSV-1, HSV-2 and VZV) thymidine kinase converts aciclovir to the aciclovir monophosphate, which is then converted to the diphosphate by cellular guanylate kinase, and finally to the triphosphate by phosphoglycerate kinase, phosphoenolpyruvate carboxykinase, and pyruvate kinase. Aciclovir triphosphate competitively inhibits viral DNA polymerase and competes with the natural deoxyguanosine triphosphate, for incorporation into viral DNA. Once incorporated, aciclovir triphosphate inhibits DNA synthesis by acting as a chain terminator. One may consider aciclovir to be a prodrug as it is metabolized to more active compounds. Aciclovir is selective and low in cytotoxicity as the cellular thymidine kinase of normal, uninfected cells does not use aciclovir effectively as a substrate.
Aciclovir (INN) or acyclovir (USAN, former BAN) is a synthetic deoxyguanosine analog and it is the prototype antiviral agent that is activated by viral thymidine kinase. The selective activity of aciclovir is due to its affinity for the thymidine kinase enzyme encoded by HSV and VZV. EC50 value of acyclovir against clinical herpes virus isolates was 1.3 μM (range: < 0.56 to 3.3 μM).
The oral bioavailability is 10% to 20%, and decreases with increasing dose. Food does not affect the absorption of acyclovir. The following are the pharmacokinetic parameters for 50 mg buccal tablet, Sitavig, in the saliva: AUC 0 - 24 hours = 2900±2400 mcg.h/mL; Cmax = 440±241 mcg/mL; Tmax = 7.95 ± 4.08 hours.
Hepatic, Acyclovir is metabolized to 9-[(carboxymethoxy)methyl]guanine (CMMG) and 8 hydroxy-acyclovir (8-OH-ACV) by oxidation and hydroxylation. It is suggested in studies that acyclovir is first metabolized to acyclovir aldehyde by alcohol dehydrogenase and then converted to CMMG. The build up of acyclovir aldehyde may be the cause of acyclovir-induced nephrotoxicity in the absence of crystalluria.
Primarily excreted unchanged by the kidneys via active tubular secretion.
Aciclovir may cause nephrotoxicity (crystallization of aciclovir within renal tubules, elevation of serum creatinine, transient), and neurotoxicity (coma, hallucinations, lethargy, seizures, tremors). Nephrotoxicity and neurotoxicity usually resolve after cessation of aciclovir therapy. However, there is no well-defined relationship between aciclovir concentrations in the blood and these adverse effects.
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