本計畫主要目的在於評估一系列新開發之Nalbuphine前驅藥長效植入微球粒劑型其生體外、生體內藥物釋放速率及其藥效學之研究。於生體外及生體內之藥物釋放結果顯示不同親水性之前驅藥對藥物釋放動力學有所影響;當前驅藥親水性增加時,藥品於生體外及生體內之釋放速率皆上升,顯示其生體內藥物釋放速率可由生體外之藥物釋放所反映出來。利用兔隻壓掌實驗可得知生體內藥物釋放快且完全的藥物其止痛效果也較佳。因而對此系列Nalbuphine前驅藥長效植入微球粒劑型而言,其藥品之物化性質---生體外/生體內藥物釋放速率---生體內藥效間有相當好的相關性。 The major purpose of this project is to develop and evaluate a series of prolong-released implantable microspheres loaded with various nalbuphine prodrugs. Three major studies were included in this project: the in vitro drug release study, in vivo pharmacokinetic study and in vivo pharmacodynamic study. The results indicate that higher in vitro and in vivo drug release rates were observed for the microspheres loaded with more hydrophilic prodrugs. The rabbit paw pressure experiments also indicate that the microspheres loaded with more hydrophilic prodrug had higher percent analgesic effect. The results suggest the different physico-chemical properties of nalbuphine prodrugs may attribute to the various in vitro/in vivo release rates from microspheres and therefore affect their pharmacodynamic performance.