Famvir
Famciclovir: a new systemic antiviral agent for herpesvirus infections.

Stott GA.

Department of Family Medicine, York Hospital, Pennsylvania, USA.

Acyclovir was the first antiviral drug approved for the treatment of herpes zoster. Several new antiviral agents have since been introduced, one of which is famciclovir. The pharmacokinetics of famciclovir allow a more convenient dosing schedule than the schedule used with acyclovir. Famciclovir is metabolized in the liver, but the P450 cytochrome system is not involved. Both acyclovir and famciclovir accelerate cutaneous healing, but studies suggest that famciclovir may reduce the severity of postherpetic neuralgia when compared with placebo. Famciclovir is currently approved only for use in immunocompetent patients, but clinical trials involving immunocompromised patients are in progress.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9166148&dopt=Abstract famciclovir Famvir



Famvir
Pretransplant famciclovir as prophylaxis for hepatitis B virus recurrence after liver transplantation.

Singh N, Gayowski T, Wannstedt CF, Wagener MM, Marino IR.

Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Veterans Affairs Medical Center, Pennsylvania 15240, USA.

Liver transplantation in patients with detectable hepatitis B virus (HBV) DNA is associated with a high rate of HBV recurrence and detectable HBV DNA is often considered a contraindication for liver transplantation. Famciclovir, an oral form of the purine nucleoside penciclovir, has been shown to inhibit HBV replication. This pilot study was conducted to determine whether a 6-month course of famciclovir, administered before transplantation, was effective in inhibiting HBV replication in patients with end-stage liver disease caused by HBV and detectable HBV DNA and to assess the posttransplant clinical and virologic outcome of patients becoming HBV DNA negative with famciclovir prior to transplantation. All eight patients enrolled were hepatitis B surface antigen (HBsAg) positive; their HBV DNA levels at baseline ranged from 4.3 to 25,321 pg/ml (mean 3,661 pg/ml). Six of the eight patients were also seropositive for HBeAg. An initial decline in HBV DNA titers occurred in all patients; however, only 25% (two of eight) of the patients became HBV DNA negative before transplantation and underwent liver transplantation. Seroconversion to hepatitis B surface antibody (HBsAb) (and HBeAb in HBeAg-positive patient) was demonstrated at the conclusion of famciclovir in the transplanted patients. Both patients remain HBV DNA negative at nearly 2 years of follow-up after transplantation. HBV DNA remained detectable in 63% (five of eight) of the patients. The mean HBV DNA level for patients who became HBV DNA negative was 5.1 pg/ml versus 424 pg/ml in nonresponders. Adverse effects attributable to famciclovir were not observed in any of the patients. Future studies should assess the predictors of response to famciclovir so that patients likely to achieve good virologic outcome can be targeted for such a therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9175803&dopt=Abstract famciclovir Famvir



Famvir
[Famciclovir plus interferon in the treatment of a patient with chronic hepatitis B and severe liver failure]

[Article in Spanish]

Piqueras B, Salcedo M, Banares R, Garcia-Duran F, Banos E, de Diego A, Roldan P, Cos E, Clemente G.

Seccion de Hepatologia, Hospital General Universitario Gregorio Maranon, Madrid.

The natural history of liver disease caused by persistent infection with hepatitis B virus (HBV) can be quite variable. The wide range of liver injury suggests a great degree of variability in the interaction between the replicating virus and possible immune responses. At the current time, Interferon is the most extensively studied antiviral agent for chronic hepatitis B, but because of the substantial number of nonresponders, relapses and side events, it continues the search of alternative therapies. Many nucleoside analogues agents have been found to have antiviral activity in vitro or in vivo. The second generation nucleoside analogues with the most promising potential at present include Famciclovir. We report the case of a patient with HBV infection in whom a reactivation of his disease lead to hepatic failure, analysing the possible pathogenic mechanisms implied and calling attention upon the excellent results achieved with a combine regimen of Interferon and Famciclovir.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9198481&dopt=Abstract famciclovir Famvir



Famvir
In vitro oxidation of famciclovir and 6-deoxypenciclovir by aldehyde oxidase from human, guinea pig, rabbit, and rat liver.

Rashidi MR, Smith JA, Clarke SE, Beedham C.

Pharmaceutical Chemistry, School of Pharmacy, University of Bradford, UK.

Famciclovir, a 9-substituted guanine derivative, is a new antiviral agent which undergoes rapid hydrolysis and oxidation in man to yield the active antiherpes agent, penciclovir. 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. In the present study the oxidation of famciclovir and 6-deoxypenciclovir with partially purified molybdenum hydroxylases from human, guinea pig, rabbit, and rat livers and bovine milk xanthine oxidase has been investigated. Famciclovir and 6-deoxypenciclovir were oxidized predominantly to 6-oxo-famciclovir and penciclovir, respectively, by human, guinea pig, and rat liver aldehyde oxidase. Small amounts of 8-oxo and 6,8-dioxo-metabolites were also formed from each substrate. Famciclovir and 6-deoxypenciclovir were good substrates for rabbit liver aldehyde oxidase but, in each case, two major metabolites were formed. 6-Deoxypenciclovir was converted to penciclovir and 8-oxo-6-deoxypenciclovir in approximately equal quantities; famciclovir was oxidized to 6-oxo-famciclovir and a second metabolite which, on the basis of chromatographic and UV spectral data, was thought to be 8-oxo-famciclovir. Two groups of Sprague Dawley rats were identified; those containing hepatic aldehyde oxidase and xanthine oxidase and those with only xanthine oxidase. These have been designated AO-active and AO-inactive rats, respectively. Famciclovir was not oxidized by enzyme from AO-inactive rats or bovine milk xanthine oxidase although 6-deoxypenciclovir was slowly converted to penciclovir by rat liver or milk xanthine oxidase. Inhibitor studies showed in human, guinea pig, and rabbit liver that xanthine oxidase did not contribute to the oxidation of famciclovir and 6-deoxypenciclovir; thus it is proposed that drug activation in vivo would be catalyzed solely by aldehyde oxidase.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9224775&dopt=Abstract famciclovir Famvir



Famvir
Antiviral efficacies of famciclovir, valaciclovir, and brivudin in disseminated herpes simplex virus type 1 infection in mice.

Wutzler P, Ulbricht A, Farber I.

Institute for Antiviral Chemotherapy, Friedrich Schiller University of Jena, Erfurt, Germany.

The animal model of necrotic hepatitis caused by HSV-1 infection in juvenile mice was used to compare the efficacies of the oral antiherpes agents famciclovir (FCV), valaciclovir (VACV) and brivudin (BVDU). The experimental infection allows the measurement of viral replication in the liver by macroscopic lesions and the evaluation of mortality from encephalitis. Mice intravenously inoculated with a highly virulent clinical HSV-1 isolate were orally treated by gavage over a period of 3 days starting on day 2 post infection. The reference drug acyclovir (ACV) was administered subcutaneously. Necrotic hepatitis was significantly (p < 0.01) reduced by treatment with FCV, VACV and ACV at a dose of 50 mg/kg per day divided into 3 doses. No significant effect was achieved with BVDU at 200 mg/kg per day. Treatment with FCV at 50 mg/kg per day, ACV at 100 mg/kg per day, and VACV at 200 mg/kg per day significantly (p < 0.001) decreased mortality in mice. BVDU treatment at 200 mg/kg per day did not reduce mortality but significantly prolonged (p < 0.05) the survival time.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9268766&dopt=Abstract famciclovir Famvir