Pharmacokinetics of Ketorolac Pentyl Ester, a Novel Ester Der1vatwe of Ketorolac, in Rabbits

Ketorolac是一個強效非固醇類抗發炎劑，最近有一個ketorolac的酯化物－戊酯ketorolac(ketorolac pentyl ester)被合成，並且當戊酯ketorolac製成注射型油劑時可有長效的作用。戊酯ketorolac是以前驅藥的設計方式且以酯化方法合成，其被預測在活體使用時應是ketorolac的前驅藥，但這點尚未被證實。本研究的目的為進行一活體動物之藥物動力學實驗來探討戊酯 ketorolac是否是ketorolac的前驅藥。本實驗以六隻白兔分別接受靜脈注射各一次等莫耳數的ketorolac及戊酯ketorolac，並偵測其藥物動力學參數。血中之ketorolac及戊酯ketorolac濃度是以高效能液相層析法來偵測。靜脈注射後，戊酯ketorolac的血漿中濃度快速下降而ketorolac被快速生成，並且戊酯ketorolac會完全轉換成ketorolac。本實驗證實在活體狀態下戊酯ketorolac是ketorolac的前驅藥。本實驗之結論如下：在白兔活體藥物動力學實驗中，戊酯ketorolac被證實是ketorolac的前驅藥。

關鍵字

ketorolac ；戊酯ketorolac ；藥物動力學；前驅藥

並列摘要

Ketorolac is a potent nonsteroidal anti-inflammatory drug. Recently, a novel ester of ketorolac, ketorolac pentyl ester, was synthesized. When prepared in injectable oil, the new agent demonstrated a long duration of action. Ketorolac pentyl ester was synthesized using a prodrug design by esterification of ketorolac, and appeared to be a prodrug of ketorolac in vivo, which needed to be confirmed. The aim of the present study was to establish the prodrug's pharmacokinetics in vivo, and to confirm whether or not ketorolac pentyl ester was a prodrug of ketorolac. Pharmacokinetic profiles of intravenous ketorolac and its pentyl ester on an equal-molar basis in six rabbits were evaluated. A high-performance liquid chromatographic method was used to determine the plasma concentrations of ketorolac and its pentyl ester. We found that the plasma concentrations of ketorolac pentyl ester declined rapidly after injection and so did the conversion of ketorolac pentyl ester to ketorolac. Also, the conversion of ketorolac was proved complete when compared with intravenous ketorolac under an equi-molar basis. In conclusion, this in vivo pharmacokinetic study confirmed that keterolac pentyl ester was a prodrug of keterolac.

並列關鍵字

ketorolac ； ketorolac pentyl ester ； pharmacokinetic ； prodrug

國際替代計量

Pharmacokinetics of Ketorolac Pentyl Ester, a Novel Ester Der1vatwe of Ketorolac, in Rabbits

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