Penciclovir

Penciclovir

Clinical data
Pregnancy category	B1 (Au), B (U.S.)
Routes of administration	Topical
ATC code	D06BB06 (WHO) J05AB13 (WHO)
Legal status
Legal status	S2 (Au)
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]- 3H-purin-6-one
CAS Number	39809-25-1
PubChem CID	4725
DrugBank	APRD00041
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C10H15N5O3
Molar mass	253.258 g/mol

Penciclovir (INN) (IPA: Template:IPA) is a guanine 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 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. Firstly, cellular thymidine kinases phosphoylate 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. Secondly, 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 is 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 relatively higher given equivalent cellular doses.