Herpes viruses penciclovir

Pharmacology Penciclovir is an antiviral agent active against herpes viruses. It has in vitro inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). 

Penciclovir [pen SIK lo veer] is an acyclic guanosine nucleoside derivative that is active against herpes simplex virus Types I and II, and against varicella-zoster virus. Penciclovir is only administered topically (Figure 37.8). Penciclovir is monophosphorylated by viral thymidine kinase, and cellular enzymes form the nucleoside triphosphate, which inhibits herpes DNA polymerase. Penciclovir triphosphate has an intracellular half-life 20 to 30 times longer than does acyclovir triphosphate (see p. 365). Penciclovir is negligibly absorbed from topical application, and is well tolerated. Both healing and pain are shortened approximately one-half day in duration, compared to placebo-treated subjects. 

Famciclovir is rapidly converted to penciclovir in intestinal and liver tissue after oral administration. More than half of an oral dose of famciclovir is excreted in the urine as unchanged penciclovir. The plasma elimination half-life of penciclovir is about 2h, similar to that of acyclovir however, the intracellular half-life of penciclovir in herpes virus-infected cells is considerably longer than that of acyclovir. 

The cream contains penciclovir, an antiviral agent active against herpes viruses for topical administration as a 1% white cream. Each gram of cream contains 10 mg penciclovir... 

Resistant variants owing to thymidine kinase or DNA polymerase mutations can be selected by passage in vitro, but the occurrence of resistance during clinical use is currently low. Thymidine kinase-deficient, acyclovir-resistant herpes viruses are cross-resistant to penciclovir. 

Acyclovir (Zovirax) and penciclovir (Denavir) are the only topical antiviral dragp currently available These dragp inhibit viral replication. Acyclovir is used in the treatment of initial episodes of genital herpes, as well as heqies simplex virus infections in immunocompromised patients (patients with an immune system incapable of fighting infection). Penciclovir is used for the treatment of recurrent herpes labialis (cold sores) in adults. 

Topical acyclovir (Zovirax) is available as a 5% ointment topical penciclovir (Denavir), as a 1% cream for the treatment of recurrent orolabial herpes simplex virus infection in immunocompetent adults. Adverse local reactions to acyclovir and penciclovir may include pruritus and mild pain with transient stinging or burning. 

The guanosine analog penciclovir is the active metabolite of famciclovir (see above). Topical application of 1% penciclovir cream is effective for the treatment of recurrent herpes labialis in immunocompetent adults (Table 49-1). When therapy was initiated within 1 hour after the onset of signs or symptoms and continued every 2 hours during waking hours for 4 days, treatment with topical penciclovir resulted in a shortening of the mean duration of lesions, lesion pain, and virus shedding by approximately one-half day compared with placebo. Side effects are uncommon. 

Herpesviruses are associated with a broad spectrum of diseases, for example, cold sores, viral encephalitis, and genital infections, the latter being a hazard to the newborn during parturition. The drugs that are effective against these viruses exert their actions during the acute phase of viral infections, and are without effect in the latent phase. Two new anti-herpes agents are penciclovir and cidofovir. 

Famciclovir is an oral prodrug of penciclovir, a selective antiviral drug with activity against Varicella zoster virus. Herpes simplex virus types 1 and 2, and Epstein-Barr virus, as well as human hepatitis B virus. 

Famciclovir is an antiherpes virus agent that converts to penciclovir, which inhibits viral DNA replication by interfering with viral DNA polymerase. It is indicated in the treatment of acute herpes zoster treatment or suppression of recurrent genital herpes in immunocompetent patients and treatment of recurrent mucocutaneous herpes simplex infections in HIV-infected patients. 

Figure 8.10 (A) Relationship between the lung uptake of [ F]-FHBG and in vitro enzyme activity of a mutant HSVl-TK. Data are were combined from two studies and were fitted to a hyperbolic equation and corresponding regression curve and are displayed. (B) Relationship between the lung uptake of [ F]-FHBG and mutant HSVl-TK enzyme activity in rats with ANTU-induced increases in pulmonary vascular permeability. [1 F]-FHBG = 9-(4-[ F]-fluoro-3-hydroxymethylbutyl)guanine, ID = injected dose, mHSVl-TK = mutant Herpes simplex virus-1 thymidine kinase, PCV = penciclovir. [Reproduced with permission from Richard et al. (71).]...

Sarisky RT, Bacon TH, Boon RJ, Duffy KE, Esser KM, Leary J, Locke LA, Nguyen TT, Quail MR, Saltzman R (2003) Profiling penciclovir susceptibility and prevalence of resistance of herpes simplex virus isolates across eleven clinical trials. Arch Virol 148(9) 1757 1769... 

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