sorivudine and Encephalitis--Viral

Antiviral treatment of herpesvirus infections is rapidly changing since the advent of new drugs with improved oral availability. The efficacy of valaciclovir, the prodrug of aciclovir, and famciclovir, the prodrug of penciclovir, in the treatment of herpes genitalis and acute herpes zoster has been well documented in large clinical trials. Both drugs are effective on zoster-associated pain. Brivudin and sorivudine which are the most active compounds against varicella-zoster virus (VZV) in cell culture have also been successful in the treatment of herpes zoster. Aciclovir is still the standard therapy of severe herpes simplex virus (HSV) and varicella virus infections. In patients treated with aciclovir, the mortality of herpes encephalitis has been reduced to about 25%. The development of resistance against aciclovir and the other nucleoside analogues has not been a problem to date in the treatment of immunocompetent individuals. However, in immunocompromised patients, aciclovir-resistant HSV strains often emerge. In such cases, intravenous foscarnet is the current treatment of choice.

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Antiviral Agents; Arabinofuranosyluracil; Bromodeoxyuridine; Chickenpox; Drug Resistance, Microbial; Encephalitis, Viral; Famciclovir; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Humans; Immunocompromised Host; Prodrugs; Simplexvirus; Valacyclovir; Valine

We compared the in vitro and in vivo antiviral effects against herpes simplex virus type 1 (HSV-1) and other biological properties of 1-beta-D-arabinofuranosyl-5-[(E)-2-chlorovinyl]uracil (CV-araU) and 1-beta-D-arabinofuranosyl-5-[(E)-2-bromovinyl]uracil (BV-araU, sorivudine). Both CV-araU and BV-araU exhibited antiviral activities against HSV-1 in the cell culture derived from mouse, though the activities were lower than those seen in human cells. For intraperitoneal and intracerebral infections in mice with HSV-1 strain WT-51, both compounds, administered twice daily, were effective in increase in the survival rate at doses of 15 mg/kg and 30 mg/kg, respectively. In pharmacokinetic analysis, both drugs were absorbed well in the rat gastrointestinal tract following oral administration. There was no difference between the metabolism of orally administered CV-araU and BV-araU in rats. High levels of the corresponding base were found in plasma after oral administration of CV-araU and BV-araU, but much lower base levels were seen after intravenous doses. Both drugs were resistant to degradation by rat liver enzymes.

Topics: 3T3 Cells; Animals; Antiviral Agents; Arabinofuranosyluracil; Bromine; Cell Line; Chlorine; Encephalitis, Viral; Herpes Simplex; Humans; Male; Mice; Rats