在天竺鼠癸酸Buprenorphine之油性藥物貯存劑型產生一個和劑量相關的長效止痛作用

The Depot of Buprenorphine Decanoate Produced a Dose-related Long-lasting Antinociceptive Effect in Guinea Pigs

背景：當病人忍受長期的疼痛煎熬時，一個長效的止痛劑是有需求的。本研究的目的是在評估癸酸buprenorphine之新的藥物貯存劑型之止痛效用及其在人類及數種動物之血液樣本中之代謝情形。方法：在以天竺鼠肌肉注射為動物模式下，癸酸buprenorphine之油性藥物貯存劑型及傳統鹽酸buprenorphine之水液劑型的止痛效用被評估。癸酸buprenorphine在人類及數種動物血液中之代謝情形也被研究。藥物之止痛效用以縮腳掌之反射來評估，血液中之藥物濃度則以高效能液相層析儀來偵測。結果：我們發現鹽酸buprenorphine（水劑）及癸酸buprenorphine（油劑）皆可產生和劑量相關的止痛作用，但二者之效期不同。在相同的給藥莫耳數0.6微莫耳／公斤下，鹽酸buprenorphine及癸酸buprenorphine之止痛效期分別為4及72小時。在人類及數種動物血液之體外代謝研究中，癸酸 buprenorphine完全代謝成為buprenorphine。癸酸buprenorphine是 buprenorphine之前趨藥。結論：在天竺鼠肌肉注射癸酸buprenorphine之油性藥物貯存劑型時，可產生一個和劑量相關的長效止痛作用，而其作用比傳統劑型還長許多，並且癸酸buprenorphine是buprenorphine之前趨藥。

Background: A long-acting analgesic may be particularly desirable in patients suffering from long-lasting pain. The aim of the study was to evaluate the antinociceptive effect of a novel depot of buprenorphine decanoate and its metabolic profiles in human and animal blood. Methods: Following their intramuscular injections in guinea pigs, the antinociceptive effects of the novel depot of buprenorphine decanoate (in oil) and the traditional dosage form of buprenorphine HC1 (in saline) were evaluated. An in vitro metabolic study of buprenorphine decanoate in human and animal blood was also carried out. The antinociception of drugs was evaluated using the plantar test. The blood concentrations of drugs were assayed using a high performance liquid chromatography. Results: We found that both the buprenorphine HC1 (in saline) and buprenorphine decanoate (in oil) produced dose-related antinociceptive effect but of different duration of action. Under an equi-mole basis of 0.6μmol/kg, the durations of action of buprenorphine HC1 and decanoate were 4 and 72 h, respectively. In in vitro metabolic study in human and animal bloods, buprenorphine decanoate was totally converted to buprenorphine. Buprenorphine decanoate is a prodrug of buprenorphine. Conclusions: Intramuscular injection of the depot of buprenorphine decanoate in guinea pigs produced a doserelated long-lasting antinociceptive effect which was much longer than that of the traditional dosage form of buprenorphine HC1. Moreover, buprenorphine decanoate is a prodrug of buprenorphine.