Affiliation:
1. Pharmos Corp., Alachua, Florida 32615.
Abstract
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference38 articles.
1. Synthesis and biological evaluation of prodrugs of zidovudine;Aggarwal S. K.;J. Med. Chem.,1990
2. Activation by thymidine kinase and potent antiherpetic activity of 2'-nor-2'-deoxyguanosine (2'NDG);Ashton W. T.;Biochem. Biophys. Res. Commun.,1981
3. Benjamin E. B. A. Firestone R Bergstrom M. Fass I. Massey I. Tsina and Y. T. Lin. 1987. Selection of a derivative of the anti
4. Improved delivery through biological membranes. 54. Synthesis, characterization and antiviral activity of a series of ribavirin chemical delivery systems: 5' and carboxamide derivatives;Bhagrath M.;Antiviral Chem. Chemother.,1991
5. Bodor N. 1987. Redox drug delivery systems for targeting drugs to VOL. 38 1994
Cited by
50 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献