一個含Ketorolac Tert-Butyl酯之藥物貯存劑型在大白鼠測試有長效之消炎及止痛作用

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

目前在臨床上並無長效之非固醇類抗發炎劑可供治療為期較長的疼痛，本研究的目的在探討一個內含Ketorolactert-butyl醋的新藥物胖存劑型是否具有長效的止痛及抗發炎作用。我們以大白鼠來進行二項實驗。實驗一：我們測量肌肉注射傳統劑型Ketorolac trometharnine水溶液的抗發炎及止痛作用。實驗二：我們測量肌肉注射含Ketorolac tert-butyl酪之新油性劑型的抗發炎及止痛作用。我們發現肌肉注射傳統Ketorolac trometharnine水劑240µmol／kg產生了顯著的止痛及抗發炎作用，但其效期僅有8小時。而肌肉注射新的Ketorolac tert-butyl酯油劑240µmol／kg卻產生了56／J、時的止痛及抗發炎作用。我們的結論為在大自鼠以肌肉注射Ketorolac tert-butyl醋之油劑可產生一個非常長的止痛及抗發炎作用，其效果為傳統Ketorolac tromethamine水劑的7倍長。

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 trometharnine were evaluated. In study 2, the antinociceptive and anti-inflammatory effects of intramuscular ketorolac tert-butyl ester were evaluated. We found that ketorolac trometharnine 240 µ mol/k:g (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/k:g (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 ofketorolac tromethamine did.