Penciclovir

Clinical data
Pronunciation	/ˌpɛnˈsaɪkloʊˌvɪər/[1]
Trade names	Denavir
AHFS/Drugs.com	Monograph
MedlinePlus	a697027
Pregnancy category	AU: B1
Routes of administration	Topical
ATC code	D06BB06 (WHO) J05AB13 (WHO)
Legal status
Legal status	AU: S2 (Pharmacy medicine) US: ℞-only
Pharmacokinetic data
Bioavailability	1.5% (oral), negligible (topical)
Protein binding	<20%
Metabolism	Viral thymidine kinase
Elimination half-life	2.2–2.3 hours
Excretion	Renal
Identifiers
IUPAC name 2-amino-9-[4-hydroxy-3-(hydroxymethyl)butyl]-1H-purin-6(9H)-one
CAS Number	39809-25-1 Y
PubChem CID	135398748
DrugBank	DB00299 Y
ChemSpider	4563 Y
UNII	359HUE8FJC
KEGG	D05407 Y
ChEBI	CHEBI:7956 Y
ChEMBL	ChEMBL1540 Y
CompTox Dashboard (EPA)	DTXSID9046491
ECHA InfoCard	100.189.687
Chemical and physical data
Formula	C10H15N5O3
Molar mass	253.262 g·mol−1
3D model (JSmol)	Interactive image
Melting point	275 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
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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 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.^{[citation needed]}