Accession Number:

ADB146391

Title:

Development of Systems for Delivery of Antiviral Drugs

Descriptive Note:

Technical Report,30 Sep 1988,14 Sep 1989

Corporate Author:

SOUTHERN RESEARCH INST BIRMINGHAM AL BIRMINGHAM United States

Report Date:

1989-10-01

Pagination or Media Count:

17.0

Abstract:

Ribavirin, a broad-spectrum antiviral agent with potent activity in vitro against a number of important RNA viruses of military significance, is severely limited in its usefulness against virus-induced encephalitic diseases because it does not cross the blood-brain barrier well enough to achieve effective antiviral concentrations in the brain. Our efforts have been directed toward the brain-specific delivery of ribavirin and other antiviral agents by means of a redox prodrug concept. The scope of the research program involves the synthesis of CNS-targeted prodrug esters of ribavirin and selenazole, pharmacokinetic studies of drug distribution and sustained delivery of drug in the brain, and the evaluation of the therapeutic efficacy of these antiviral prodrugs compared with the parent drugs in the treatment of lethal Venezuelan equine encephalitis VEE virus, Japanese encephalitis JE virus, and Punto Turo PT virus infections in mice. In preliminary studies at USAMRIID, the initial ribavirin prodrug protected mice from a lethal challenge of JE virus and was much superior in efficacy to the parent drug which had no effect. Keywords Antiviral drugs, Ribavirin, Japanese encephalitis, Prodrug esters, Brain-specific drug targeting, Drug delivery.

Subject Categories:

Distribution Statement:

APPROVED FOR PUBLIC RELEASE