Depot of Ketorolac Tert-butyl Ester Has Long-acting Antinociceptive and Anti-inflammatory Effects in Rats

Abstract

Currently, no long-acting nonsteriodal anti-inflammatory drug is available clinically for the treatment of long-lasting pain. The aim of the study was to evaluate the antinociceptive and anti-inflammatory effects and durations of actions of a novel depot formulation of ketorolac tert-butyl ester and to observe whether this depot formulation had a long-acting effect. Two studies in Sprague-Dawley rats were carried out. In study 1, the antinociceptive and anti-inflammatory effects of intramuscular ketorolac tromethamine were evaluated. In study 2, the antinociceptive and anti-inflammatory effects of intramuscular ketorolac tert-butyl ester were evaluated. We found that ketorolac tromethamine 240 μ mol/kg (in saline) produced significant antinociceptive and anti-inflammatory effects with duration of action of 8 h. Ketorolac tert-butyl ester at a dose of 240 μ mol/kg (in oil) produced significant long-acting antinociceptive and anti-inflammatory effects with duration of action of 56 h. We conclude that intramuscular injection of a novel depot formulation of ketorolac tert-butyl ester in rats produced long-acting antinociceptive and anti-inflammatory effects which were 7-fold longer than the traditional dosage form of ketorolac tromethamine did.