在大白鼠測試Ketorolac丙酸酯的五種藥物貯積劑型之止痛及抗發炎效果

The Antinociceptive and Anti-inflammatory Effects of Five Depot Formulations of Ketorolac Propyl Ester in Rats

背景：Ketorolac是一^固強效的非類固醇抗發炎藥。近日來，本實驗室合成了一個ketorolac前驅 藥：ketorolac丙酸酯。本研究的目的在評估ketorolac丙酸酯的五種藥物貯積劑型之止痛及抗發 炎效果。這五種劑型之載體分別為注射用芝麻油，花生油，大旦油，蓖麻油，及棉花仔油。 傳統劑型ketorolac tromethamine水劑被用來做對照組。方法：共有六組實驗於大白鼠進行，先以ketorolac丙酸酯溶於五種油性載體作為肌肉注射（240 jimol/kg），再於腳掌注射carrageenin造成疼痛及發炎反應，爾後觀察其止痛及消炎作用。結果：傳統劑型ketorolac tromethamine水劑產生8小時的止痛及抗發炎作用，而以ketorolac丙酸酯製成之五種藥物貯積劑型皆有較長效之止痛及抗發炎作用，其效期為54至78小時。而當以 棉花仔油作為載體，其止痛及抗發炎效期為78小時。結論：以ketorolac丙酸酯製成之五種藥物貯積劑型皆有長效之止痛及抗發炎作用。

Background: Ketorolac is a potent nonsteroidal anti-inflammatory drug. Recently, a ketorolac prodrug, ketorolac propyl ester, was synthesized in our laboratory. The aim of the study was to evaluate the antinociceptive and anti-inflammatory effects of ketorolac propyl ester in five depot formulations. The vehicles used in these for-mulations were injectable vegetable oils, i.e., sesame oil, peanut oil, soybean oil, castor oil, and cottonseed oil. The traditional therapentic form of ketorolac tromethamine in saline was used as control. Methods: Six studies were carried out to test the antinociceptive and anti-inflammatory effects of intramuscular ketorolac tromethamine (in saline) and its propyl ester (in five depot formulations) 240 jimol/kg on Sprague- Dawley rats treated with intraplantar carrageenin. Results: Ketorolac tromethamine (in saline) produced an 8 h duration of action on both antinociception and anti-inflammation, whereas ketorolac propyl ester in five oily vehicles produced 54- to 78-h durations of actions in both antinociception and anti-inflammation. Ketorolac propyl ester in cottonseed oil produced a duration of action of 78h in both antinociception and anti-inflammation. Conclusions: All five depot formulations of ketorolac propyl ester produced longer durations of antinociceptive and anti-inflammatory effects.