Prodrug chemical delivery systems

Capecitabine is an example of a prodrug chemical delivery system that requires a series of enzymatic steps for conversion to the active antitumor drug species. S-fluorouracil (Scheme 5-24). Tumors located in tissues with high levels of the required enzymes. should respond best to treaunent with capecitabine. Esterase activity occurs primarily in the liver, allowing the intact e.ster capecitabine to be the absorbed species following oral administration. The ester hydrolysis product itself shows some specific toxicity towani... 

Classical carrier-linked prodrugs Site-specific chemical delivery systems Macromolecular prodrugs Drug-antibody conjugates... 

A special group of carrier-linked prodrugs are the site-specific chemical delivery systems [23], Macromolecular prodrugs are synthetic conjugates of drugs covalently bound (either directly or via a spacer) to proteins, polypeptides, polysaccharides, and other biodegradable polymers [24],... 

The oxidation of dihydropyridine-based chemical delivery systems (CDSs) pioneered by Bodor and co-workers [176] has been discussed in a previous book (Chapt. 13 in [81]). There, we examined the principles by which such compounds function to deliver drugs to the brain. Here, we focus our attention to the last step in the activation of these double prodrugs, namely hydrolysis to release the drug. 

E. Shek, Chemical Delivery Systems and Prodrugs of Anticonvulsive Drugs , Adv. Drug Delivery Rev. 1994, 14, 227-241. 

By the term chemical delivery system (CDS) we shall here refer to all derivatives of a parent drug which enhance access to the intended site of action by modification of physicochemical properties, and which deliver the parent by chemical or enzymic action in the biophase itself. The term prodrug is also often used, but this term really has a wider meaning ... 

N. Bodor and J. J. Kaminski, Prodrugs and site-specific chemical delivery systems, Annu. Rep. Med. Chem. 22 303 (1987). 

As indicated in Chapter 15, the development of genomics and proteomics will undoubtedly provide further information of the differential experessions of enzymes in diseased and normal tissues. This will allow the future development of prodrug-based chemical delivery systems to target specific cell types through the use of the upregulated enzymes in diseased tissues to release the active drag. 

The prodrug methenamine, described above in this chapter (Scheme S-17), can be considered a site-specific chemical delivery system for the urinary tract antiseptic agent fotmal-dehyde. The low pH of the urine promotes the hydrolysis... 

Tissue targeting may also be directed at tumors through the use of monoclonal antibodies, as briefly mentioned earlier. Finally, brain targeting can also be attempted with the prodrug approach, as exemplified by estradiol by use of a redox-based chemical delivery system (174). 

V. J. Stella, Prodrugs An overview and definition, in Prodrugs in Novel Drug Delivery Systems (T. Higuchi and V. Stella, eds.), American Chemical Society, Washington, DC, 1975, p. 1. 

H. Bundgaard, C. Larsen, E. Arnold, Prodrugs as Drug Delivery Systems XXVII. Chemical Stability and Bioavailability of a Water-Soluble Prodrug of Metronidazole for Parenteral Administration , Int. J. Pharm. 1984, 18, 79-87. 

N. M. Nielsen, H. Bundgaard, Prodrugs as Drug Delivery Systems. 68. Chemical and Plasma-Catalyzed Hydrolysis of Various Esters of Benzoic Acid A Reference System for Designing Prodrug Esters of Carboxylic Acid Agents , Int. J. Pharm. 1987, 39, 75-85. 

Bundgaard, H., C. Larsen, and E. Arnold. 1984a. Prodrugs as drug delivery systems. XXVII. Chemical stability and bioavailability of a water-soluble prodrug of metronidazole for parenteral administrated. 

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