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Galactosyl prodrug of ketorolac: synthesis, stability, and pharmacological and pharmacokinetic evaluations.

Authors :
Curcio A
Sasso O
Melisi D
Nieddu M
La Rana G
Russo R
Gavini E
Boatto G
Abignente E
Calignano A
Rimoli MG
Source :
Journal of medicinal chemistry [J Med Chem] 2009 Jun 25; Vol. 52 (12), pp. 3794-800.
Publication Year :
2009

Abstract

Although ketorolac is one of the most potent anti-inflammatory and analgesic drugs, its use has been strongly limited owing to the high incidence of adverse effects reported, particularly in the gastrointestinal tract. Using the prodrug approach, which allows the reduction of toxicological features of the parent drug without altering its pharmacological properties, we synthesized an orally administrable prodrug of ketorolac by means of its reversible conjugation to D-galactose (ketogal). In a single dose study, its pharmacokinetic profile was compared with that of ketorolac. Moreover, we found that this prodrug was able to maintain the anti-inflammatory and the analgesic activity of the drug without giving rise to gastric ulcer formation. Thus, these results indicate that ketogal is a highly effective and valid therapeutic alternative to ketorolac itself.

Details

Language :
English
ISSN :
1520-4804
Volume :
52
Issue :
12
Database :
MEDLINE
Journal :
Journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
19459639
Full Text :
https://doi.org/10.1021/jm900051r