Penciclovir is a guanine analogue antiviral drug

Antiviral drug

Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...

 used for the treatment of various herpesvirus infections. It is a nucleoside analogue

Nucleoside analogues

Nucleoside analogues are a range of antiviral products used to prevent viral replication in infected cells. The most commonly used is Acyclovir, although its inclusion in this category is uncertain, as it contains only a partial nucleoside structure, as the sugar ring is replaced by an open-chain...

 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

National Drug Code

The National Drug Code is a unique product identifier used in the United States for drugs intended for human use. The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration with a current list of all drugs manufactured, prepared, propagated,...

 0135-0315-52), Vectavir and Fenistil. Famciclovir

Famciclovir

Famciclovir is a guanine analogue antiviral drug used for the treatment of various herpesvirus infections, most commonly for herpes zoster . It is a prodrug form of penciclovir with improved oral bioavailability...

 is a prodrug

Prodrug

A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...

 of penciclovir with improved oral bioavailability.

Efficacy

In herpes labialis

Herpes labialis

Herpes labialis or "orolabial herpes" is an infection of the lip by herpes simplex virus . An outbreak typically causes small blisters or sores on or around the mouth commonly known as cold sores or fever blisters...

, the shortening of duration of healing, pain and detectable virus is maximally one day., compared with the total duration of 2-3 weeks of disease presentation.

Mode of action and selectivity

Penciclovir is inactive in its initial form. Within a virally infected cell a viral thymidine kinase

Thymidine kinase

Thymidine kinase is an enzyme, a phosphotransferase : 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, . It can be found in most living cells. It is present in two forms in mammalian cells, TK1 and TK2...

 adds a phosphate

Phosphate

A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

 group to the penciclovir molecule; this is the rate-limiting step in the activation of penciclovir. Cellular (human) kinase

Kinase

In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...

s then add two more phosphate groups, producing the active penciclovir triphosphate. This activated form inhibits viral DNA polymerase

DNA polymerase

A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....

, 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

Cytotoxicity

Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are a chemical substance, an immune cell or some types of venom .-Cell physiology:...

 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

Aciclovir

Aciclovir or acyclovir , chemical name acycloguanosine, abbreviated as ACV,is a guanosine analogue antiviral drug, marketed under trade names such as Cyclovir, Herpex, Acivir, Acivirax, Zovirax, and Zovir...

. 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.