Disease relevance of Vectavir

• Penciclovir cream for the treatment of herpes simplex labialis. A randomized, multicenter, double-blind, placebo-controlled trial. Topical Penciclovir Collaborative Study Group [1].
• CONCLUSIONS: Penciclovir cream is the first treatment to clearly demonstrate an impact on the course of recurrent herpes labialis in immunocompetent patients [1].
• Faster healing and pain resolution occurred both among patients who first applied penciclovir cream in the prodrome and erythema stages and among those who started treatment in the papule and vesicle lesion stages [1].
• Acyclovir, penciclovir, and their prodrugs have been widely used during the past two decades for the treatment of herpesvirus infections [2].
• Antiviral strategies available at present, including interferon-alpha, have only limited efficacy, leading us to analyse the antiviral effects of penciclovir and famciclovir in the duck hepatitis B virus (DHBV) model of HBV infection in vitro and in vivo [3].

High impact information on Vectavir

• Pain (median, 3.5 days vs 4.1 days; HR, 1.22; 95% CI, 1.09-1.36; P<.001) and lesion virus shedding (median, 3 days vs 3 days; HR, 1.35; 95% CI, 1.10-1.64; P=.003) also resolved more quickly for penciclovir-treated patients compared with patients who applied the vehicle control [1].
• In DHBV-infected duck hepatocytes, penciclovir effectively inhibited viral replication, with a concentration giving half-maximal inhibition of 0.25 microM [3].
• Synergistic inhibition of hepadnaviral replication by lamivudine in combination with penciclovir in vitro [4].
• Lamivudine ([-]-beta-L-2',3'-dideoxy-3'-thiacytidine [3TC]) and penciclovir (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine [PCV]) are potent inhibitors of hepatitis B virus (HBV) replication [4].
• Cessation of antiviral prophylaxis resulted in reversion of this patient's HSV-2 isolates to acyclovir and penciclovir sensitivity, although resistant virus reappeared when antiviral prophylaxis was resumed [5].

Chemical compound and disease context of Vectavir

• However, for penciclovir, ganciclovir, brivudin, and S2242, major differences in the sensitivity of MHV-68 and EBV were observed, suggesting that MHV-68 is not always an optimal surrogate for the study of antiviral strategies for EBV [6].
• Long-term therapy with the guanine nucleoside analog penciclovir controls chronic duck hepatitis B virus infection in vivo [7].
• In vitro antiviral activity of penciclovir, a novel purine nucleoside, against duck hepatitis B virus [8].
• MATERIALS AND METHODS: The androgen independent, metastatic prostate cancer cell lines CL1 and CL1-GFP were stably transfected with the mutant HSV1-tk gene pcDNA3.1/pCMV-sr39tk, which has increased ability to phosphorylate penciclovir [9].
• CLINICAL RELEVANCE: Cidofovir and penciclovir treatments may prove to be effective against epithelial keratitis [10].

Biological context of Vectavir

• Over the likely therapeutic dose range of famciclovir 125 mg to 750 mg, the pharmacokinetics of penciclovir are linear [11].
• The bioavailability of penciclovir, measured by urinary recovery, is approximately 60% and is not affected by food [11].
• In uninfected cells incubated with 10 microM acyclonucleoside for 4 h, no phosphorylation of either BRL 39123 or acyclovir was detected [12].
• Penciclovir is a selective inhibitor of hepatitis B virus replication in cultured human hepatoblastoma cells [13].
• Cytomegalovirus was relatively resistant to BRL 39123 (IC50, 51 micrograms/ml), but equid herpesvirus 1, bovid herpesvirus 2, and felid herpesvirus 1 were susceptible (IC50S, 1.6, 1.2, and 0.9 micrograms/ml, respectively) [14].

Anatomical context of Vectavir

• In mice infected intraperitoneally with HSV-1, BRL 39123 was 10-fold more potent than ACV and a single dose of BRL 39123 reduced virus replication within the peritoneal cavity more effectively than 3 doses of ACV given 1, 5, and 20 h after infection [15].
• Studies with human liver cytosol have indicated that the oxidation of the penultimate metabolite, 6-deoxypenciclovir, to penciclovir is catalyzed by the molybdenum hydroxylase, aldehyde oxidase [16].
• Lack of effect of treatment with penciclovir or acyclovir on the establishment of latent HSV-1 in primary sensory neurons in culture [17].
• Penciclovir was distributed into tissues with an overall mean volume of distribution of approximately 1.5 l.kg-1, i.e. approximately double that of body water [18].
• These results may have implications for issues of penciclovir action and resistance, for drug resistance in the clinic, and for the interactions of herpes viruses with the peripheral and central nervous systems [19].

Associations of Vectavir with other chemical compounds

• Plasma and urine specimens were analyzed for concentrations of penciclovir, the antivirally active metabolite of famciclovir, by reverse-phase HPLC [20].
• Antiherpetic activity of (1'S,2'R)-9-([1',2'-bis(hydroxymethyl)cycloprop-1'yl]methyl)guanine (A-5021) was compared with those of acyclovir (ACV) and penciclovir (PCV) in cell cultures [21].
• A putative PT was also studied in the transient transfection system and appeared similar to the TK in phosphorylating GCV and conferring sensitivity to GCV, but not in BVdU- or PCV-mediated cell killing [22].
• Famciclovir, a synthetic acyclic guanine derivative, is a prodrug which, after oral administration, is rapidly metabolised to the highly bioavailable antiviral compound penciclovir [23].
• The ganciclovir-, penciclovir- and valaciclovir-resistant isolates also contained mutations within MCMV M97 identical or similar to recognized GCV-resistant mutations of HCMV UL97 protein kinase, and demonstrated cross-resistance to antivirals of the same class [24].

Gene context of Vectavir

• We have amplified, cloned and sequenced the gene encoding the thymidine kinase (TK) of a wild-type strain (Ab4) of equine herpesvirus-1 (EHV-1) and two mutants with defective TK activity isolated for resistance to penciclovir (PCV) [25].
• Famciclovir was much more stable than BRL 43599 in human duodenal contents (half-lives, greater than 2 h and 7 min, respectively) yet was efficiently converted to penciclovir by the tissue homogenates [26].
• BRL 39123 was inactive against an HSV-1 strain which does not express thymidine kinase activity, but a DNA polymerase mutant selected for resistance to ACV was sensitive to BRL 39123 (IC50, 1.5 micrograms/ml) [14].
• CONCLUSIONS: Three mutations within the HBV polymerase gene were detected which were associated with a reduced penciclovir sensitivity [27].
• Penciclovir (PCV) and acyclovir are acyclic guanine analogs which inhibit herpes simplex virus (HSV) DNA polymerase [28].

Analytical, diagnostic and therapeutic context of Vectavir

• Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxy-methylbut-1-yl)guanine (BRL 39123) in cell culture [14].
• Before systemic administration to infected animals, BRL 39123 and ACV were administered orally and subcutaneously to mice, and the blood was assayed for each compound by high-pressure liquid chromatography [15].
• The antiviral activity of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) was assessed in several animal models of herpes simplex virus (HSV) infection [15].
• After treatment of HSV-infected cultures for short periods, BRL 39123 was considerably more effective than ACV at reducing virus replication, and furthermore, after removal of extracellular BRL 39123, virus replication remained depressed for long periods, whereas such persistent activity was not observed with ACV [14].
• OBJECTIVES: To measure the contribution of stratum corneum barrier and microvascular perfusion in determining dermal tissue levels of hydrophilic drugs (aciclovir and penciclovir) in vivo [29].

References