Galactosyl Prodrug of Ketorolac: Synthesis, Stability, and Pharmacological and Pharmacokinetic Evaluations

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• 作者：Annalisa Curcio ; Oscar Sasso ; Daniela Melisi ; Maria Nieddu ; Giovanna La Rana ; Roberto Russo ; Elisabetta Gavini ; Gianpiero Boatto ; Enrico Abignente ; Antonio Calignano ; Maria Grazia Rimoli
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：June 25, 2009
• 年：2009
• 卷：52
• 期：12
• 页码：3794-3800
• 全文大小：163K
• 年卷期：v.52,no.12(June 25, 2009)
• ISSN：1520-4804

文摘

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.