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

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 antiinflammatory
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.