|Systematic (IUPAC) name|
|Bioavailability||1.5% (oral), negligible (topical)|
|Metabolism||Viral thymidine kinase|
|ATC code||D06 J05|
|Mol. mass||253.258 g/mol|
|(what is this?)|
Penciclovir (INN) // is a guanosine analogue antiviral drug used for the treatment of various herpesvirus infections. It is a nucleoside analogue which exhibits low toxicity and good selectivity. Because penciclovir is absorbed poorly when given orally (by mouth) it is used more as a topical treatment, and is the active ingredient in the cold sore medications Denavir (NDC 0135-0315-52), Vectavir and Fenistil. Famciclovir is a prodrug of penciclovir with improved oral bioavailability.
Mode of action and selectivity
Penciclovir is inactive in its initial form. Within a virally infected cell a viral thymidine kinase adds a phosphate group to the penciclovir molecule; this is the rate-limiting step in the activation of penciclovir. Cellular (human) kinases then add two more phosphate groups, producing the active penciclovir triphosphate. This activated form inhibits viral DNA polymerase, thus impairing the ability of the virus to replicate within the cell.
The selectivity of penciclovir may be attributed to two factors. First, cellular thymidine kinases phosphorylate the parent form significantly less rapidly than does the viral thymidine kinase, so the active triphosphate is present at much higher concentrations in virally infected cells than in uninfected cells. Second, the activated drug binds to viral DNA polymerase with a much higher affinity than to human DNA polymerases. As a result, penciclovir exhibits negligible cytotoxicity to healthy cells.
The structure and mode of action of penciclovir are very similar to that of other nucleoside analogues, such as the more widely used aciclovir. A difference between aciclovir and penciclovir is that the active triphosphate form of penciclovir persists within the cell for a much longer time than the activated form of aciclovir, so the concentration within the cell of penciclovir will be higher given equivalent cellular doses.
Spirocyclic derivative of Meldrum's acid.
- Farmaceutiska Specialiteter i Sverige - the Swedish official drug catalog. [http://www.fass.se Fass.se --> Vectavir. Retrieved on August 12, 2009. Translated from "Tiden för läkning, smärta och påvisbart virus förkortas med upp till ett dygn."
- Choudary, B. M.; Geen, G. R.; Kincey, P. M.; Parratt, M. J.; Robert, J.; Dales, M.; Johnson, G. P.; O'Donnell, S.; Tudor, D. W.; Woods, N. (1996). "A Direct Approach to the Synthesis of Famciclovir and Penciclovir". Nucleosides and Nucleotides 15 (5): 981. doi:10.1080/07328319608002029.