Accession Number : ADB152222

Title :   Development of Systems for Delivery of Antiviral Drugs.

Descriptive Note : Final rept. 30 Sep 85-14 Sep 89,

Corporate Author : SOUTHERN RESEARCH INST BIRMINGHAM AL

Personal Author(s) : Shannon, William M. ; Secrist, John A., III ; Hollingshead, Melinda G. ; Noker, Patricia E.

Report Date : OCT 1989

Pagination or Media Count : 58

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 Toro (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 superior in efficacy to the parent drug.

Descriptors :   *ANTIVIRAL AGENTS, *JAPANESE ENCEPHALITIS, BARRIERS, BLOOD, BRAIN, BROADBAND, DELIVERY, DRUGS, IN VITRO ANALYSIS, JAPANESE ENCEPHALITIS, LETHALITY, MICE, PHARMACOKINETICS, POTENCY, SPECTRA, THERAPY, VENEZUELAN EQUINE ENCEPHALOMYELITIS VIRUS, VIRUS DISEASES, MILITARY MEDICINE, MILITARY PERSONNEL, RIBONUCLEIC ACIDS.

Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE