一個含非類固醇消炎劑之長效藥物貯存劑型——Ketorolac苯酯在大白鼠之止痛與抗發炎測試

The Antinociceptive and Anti-inflammatory Effects of a Long-acting Depot Formulated Ketorolac in Rats

背景：目前在臨床上並無長效之非類固醇消炎劑可供治療為期較長的疼痛，本研究的目的在 探計一個內含ketorolac苯酯的新藥物辟存劑型是否具有長效的消炎及止痛作用。方法：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 trome-thamine 水溶液的消炎及止痛作用。實驗二 ：我們測量肌肉注射含ketorolac苯酯之新油性劑型 的消炎及止痛作用。止痛作用以腳掌壓力試驗來測試，消炎作用以腳掌腫脹試驗來測試。結果：我們發現肌肉注射傳統ketorolac tromethamine水劑24，80及240 |imol/kg產生了顯著的止痛 及消炎作用，但其效期僅有6-8小時。而肌肉注射新的ketorolac苯酯油劑240 pmol/kg卻產生了 56小時的止痛及消炎作用。結論：在大白鼠以肌肉注射ketorolac苯酯之油劑可產生一個非常長的止痛及消炎作用，其效 果為傳統ketorolac tromethamine水劑的7倍長。

Background: Currently, no long-acting nonsteroidal anti-inflammatory drug is available clinically for the treat-ment of long-lasting pain. The aim of the study was to evaluate the antinociceptive and anti-inflammatory effects and duration of action of a novel depot formulation of ketorolac benzyl ester in sesame oil. Methods: Two studies in Sprague-Dawley rats were carried out. In study 1, the antinociceptive and anti-in- flammatory effects of intramuscular ketorolac tromethamine were evaluated. In study 2, the antinociceptive and anti-inflammatory effects of intramuscular ketorolac benzyl ester were evaluated. The antinociceptive effect was evaluated using the paw pressure test, whereas the anti-inflammatory effect was evaluated by the paw edema test. Results: Intramuscular ketorolac tromethamine at 24, 80, and 240 jimol/kg (in saline) produced significant anti-nociceptive and anti-inflammatory effects with duration of action around 6 to 8 h. Ketorolac benzyl ester at a dose of 240 jimol/kg (in oil) produced significant long-acting antinociceptive and anti-inflammatory effects with dur-ation of action of 56 h. Conclusions: Intramuscular injection of ketorolac benzyl ester (in sesame oil) in rats produced antinocicep-tive and anti-inflammatory effects which were 7-fold longer in duration of action than ketorolac tromethamine (in saline).