探討Ketorolac丙基及戊基酯在天竺鼠之抗發炎效果

The Anti-inflammatory Effect of Ketorolac Propyl Ester and Pentyl Ester in Guinea Pigs

為了研發長效的非固醇類抗發炎劑，我們在天竺鼠進行研究探討Ketorolac丙基及戊基酯之藥物貯積劑型的抗發炎效果並觀察這些劑型是否有長效作用。共進行兩個實驗，實驗一，我們測量肌肉注射K自rolac傳統劑型之劑量反應。實驗二，我們測量肌肉注射新劑型K帥，ro！ac丙基及戊基酯之藥物貯積劑型之劑量反應。我們發現傳統劑型及新劑型皆可產生和劑量相關之抗發炎效果，但新劑型有較長效之作用。在給予劑量80及160mmol／kg的條件下，藥物的作用期長短分別為Ketorolactromethamine 8及10小時，Ketorolac丙基酯52及56小時，Ketorolac戊基酯80及96小時，結諸如下：新型Keto叩lac丙基輔及戊基酯之藥物貯積劑型在天竺鼠測試具有長效之作用，本研究資料將有助於開發Ketorolac酯之長效藥物貯積劑型。

In order to develop long-acting nonsteroidal antiinflammatory drugs for clinical use, we carried out two studies in guinea pigs to evaluate the antiinflammatory effects of the depots of two ketorolac esters - propyl ester and pentyl ester - and to see whether they had a long-acting effect. In study 1, the dose response study of the antiinflammatory effect of intramuscular ketorolac tromethamine in saline was carried out. In study 2, the dose response studies of the antiinflammatory effect of intramuscular ketorolac propyl ester and pentyl ester in oil were made. We found that both the traditional dosage form of ketorolac tromethamine in saline and the novel dosage forms of ketorolac esters in oil produced significant dose-related antiinflammatory effects but with different durations of action. Under the given doses of 80 and 160 mmol/kg, the durations of action of ketorolac tromethamine, ketorolac propyl ester, and pentyl ester were 8- and 10-h, 52- and 56-h, and 80- and 96-h, respectively. In conclusion, intramuscular injection of novel depots of ketorolac propyl ester and pentyl ester in guinea pigs produced a long-acting effect. These evidences are valuable for the development of long-acting depots of ketorolac esters.