Intravenous infusion of Cereport increases uptake and efficacy of acyclovir in herpes simplex virus-infected rat brains

The outcome of herpes simplex virus (HSV) infections manifesting as encepha litis in healthy or immunocompromised individuals is generally very poor wi th mortality rates of about 8 to 28% with treatment. The long-term prognosi s of survivors is often problematic, posing the need for alternative treatm ents that may decrease the mortality and morbidity associated with herpes e ncephalitis. This study addresses one such approach that includes a tempora ry permeabilization of the blood-brain barrier during treatment with acyclo vir (ACV). In these studies we utilized a synthetic bradykinin analog, Cere port (RMP-7), in conjunction with ACV to treat HSV infection of the brain i n a rat model. Cereport, infused intravenously via the jugular vein, was sh own to increase [C-14]ACV uptake in both the HSV-1-infected and -uninfected rat brain by approximately two- to threefold, correlating with enhanced ef ficacy of ACV in various brain compartments. In another series of experimen ts to determine efficacy, various doses of unlabeled ACV were administered during infusion with RMP-7. The decrease in viral titers in the temporal re gions of the brain after 5 days of treatment suggested that this approach e nhanced the efficacy of ACV treatment. These data indicated that Cereport i nfused with ACV enhances both the penetration and efficacy of this drug in the treatment of an experimental HSV-I infection of the rat brain.