Enhanced delivery of ganciclovir to the brain through the use of redox targeting
| Autor: | K Raghavan, E. Pop, M. E. Brewster, N Bodor |
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| Rok vydání: | 1994 |
| Předmět: |
Drug
Ganciclovir Chemical Phenomena media_common.quotation_subject Central nervous system Pharmacology Redox Rats Sprague-Dawley Drug Delivery Systems Drug Stability Pharmacokinetics In vivo medicine Animals Distribution (pharmacology) Tissue Distribution Pharmacology (medical) Chromatography High Pressure Liquid media_common Chemistry Physical Chemistry Brain virus diseases Hydrogen-Ion Concentration Rats Infectious Diseases medicine.anatomical_structure Blood-Brain Barrier Spectrophotometry Ultraviolet Delivery system Oxidation-Reduction Research Article medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 38:817-823 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Enhanced delivery of ganciclovir to the brain was demonstrated by a redox-based chemical delivery system. A ganciclovir monoester in which a 1-methyl-1,4-dihydronicotinate was covalently attached to one of the hydroxymethyl functions was prepared. The stability of the ganciclovir chemical delivery system (DHPG-CDS) was evaluated in aqueous buffers and organ homogenates. In vivo distribution studies in the rat indicated that while ganciclovir poorly penetrated into the central nervous system and was rapidly eliminated, DHPG-CDS provided for therapeutically relevant (2.7 microM) and sustained levels of the parent compound through 6 h. An analysis of the area under the concentration curve indicated that the chemical delivery system delivered five times more ganciclovir than that of the parent drug. The high levels in the brain and reduced levels in the blood gave a brain-to-blood drug concentration ratio of 2.54 for ganciclovir when delivered by the chemical delivery system, compared to a ratio of 0.063 when the parent drug was administered. These data suggest that DHPG-CDS could be a useful adjunct for the treatment of cytomegalovirus encephalitis. |
| Databáze: | OpenAIRE |
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