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Galactosyl prodrug of ketorolac: synthesis, stability, and pharmacological and pharmacokinetic evaluations.
- 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.
- Subjects :
- Analgesics chemical synthesis
Analgesics chemistry
Analgesics pharmacokinetics
Analgesics pharmacology
Animals
Anti-Inflammatory Agents, Non-Steroidal chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal chemistry
Dose-Response Relationship, Drug
Edema chemically induced
Hydrogen-Ion Concentration
Ketorolac adverse effects
Ketorolac chemistry
Mice
Molecular Conformation
Pain chemically induced
Prodrugs chemical synthesis
Prodrugs chemistry
Stomach Ulcer chemically induced
Time Factors
Anti-Inflammatory Agents, Non-Steroidal pharmacokinetics
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Galactose chemistry
Ketorolac pharmacokinetics
Ketorolac pharmacology
Prodrugs pharmacokinetics
Prodrugs pharmacology
Subjects
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