Penciclovir

Penciclovir 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 more often used as a topical treatment. It is the active ingredient in the cold sore medications Denavir (NDC 0135-0315-52), Vectavir and Fenivir. Famciclovir is a prodrug of penciclovir with improved oral bioavailability.

Penciclovir
Clinical data
Pronunciation/ˌpɛnˈsaɪkloʊˌvɪər/[1]
Trade namesDenavir
AHFS/Drugs.comMonograph
MedlinePlusa697027
Pregnancy
category
  • AU: B1
Routes of
administration		Topical
ATC code
Legal status
Legal status
  • AU: S2 (Pharmacy medicine)
  • US: ℞-only
Pharmacokinetic data
Bioavailability1.5% (oral), negligible (topical)
Protein binding<20%
MetabolismViral thymidine kinase
Elimination half-life2.2–2.3 hours
ExcretionRenal
Identifiers
IUPAC name
  • 2-amino-9-[4-hydroxy-3-(hydroxymethyl)butyl]-1H-purin-6(9H)-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.189.687
Chemical and physical data
FormulaC10H15N5O3
Molar mass253.262 g·mol−1
3D model (JSmol)
Melting point275 to 277 °C (527 to 531 °F)
SMILES
  • O=C2/N=C(\Nc1n(cnc12)CCC(CO)CO)N
InChI
  • InChI=1S/C10H15N5O3/c11-10-13-8-7(9(18)14-10)12-5-15(8)2-1-6(3-16)4-17/h5-6,16-17H,1-4H2,(H3,11,13,14,18) Y
  • Key:JNTOCHDNEULJHD-UHFFFAOYSA-N Y
  (verify)

Penciclovir was approved for medical use in 1996.[2]

Medical use

In herpes labialis, the duration of healing, pain and detectable virus is reduced by up to one day,[3] compared with the total duration of 2–3 weeks of disease presentation.

Mechanism of action

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.

See also

References
  1. "Penciclovir". Merriam-Webster Dictionary. Retrieved 2016-01-22.
  2. Long SS, Pickering LK, Prober CG (2012). Principles and Practice of Pediatric Infectious Disease. Elsevier Health Sciences. p. 1502. ISBN 978-1437727029.
  3. 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."
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