長效Nalbuphine製劑止痛效果之評估

The Antinociceptive Effect of a Long-acting Nalbuphine Preparation in Rabbits

背景：當病人有長期的疼痛時，長效止痛劑是有需求的。本研究之目的在評估一個Nalbuphine的新劑型（油性注射液）之止痛作用及效用長短，檢視其是否為一長效製劑。方法：我們使用雄性紐西蘭白兔（每組6隻），我們進行二項實驗。實驗一：我們研究傳統製劑鹽酸Nalbuphine 25，50及100微莫耳／公斤肌肉注射之止痛作用。實驗二 ：我們研究新型油性注射液Nalbuphine 100，200及400微莫耳／公斤肌肉注射之止痛作用。在實驗中賦形劑如：生理食鹽水（實驗一）及注射用芝麻油（實驗二）皆被使用於控制組中。我們採壓掌試驗來偵測藥物的止痛作用。結果：我們發現鹽酸Nalbuphine25，50及100微莫耳／公斤產生和劑量相關之止痛作用，而止痛效期為1，1及1.3小時。新型Nalbuphine油性注射液100，200及400微莫耳／公斤亦產生止痛作用，但效期較長，分別為8，24及48小時。在相同的給藥劑量下（100微莫耳／公斤），新型注射液比傳統注射液延長了6倍的止痛效期。結論：肌肉注射新型Nalbuphine油性注射液比肌肉注射鹽酸Nalbuphine有更長的止痛療效。

Background: An analgesic with a long-lasting effect is particularly desirable to patients suffering from longstanding pain. The aim of this study was to evaluate the antinociceptive effect and duration of action of an oily dosage form of nalbuphine base and to see whether its effect could last longer compared with nalbuphine HCI.Methods: Male New Zealand White rabbits (n = 6 in each group) were used. Two studies were carried out. In study 1, we evaluated the antinociceptive effect of intramuscular nalbuphine HCI (in saline) with dosages of 25, 50, and 100 μmol/kg. In study 2, we evaluated the antinociceptive effects of intramuscular nalbuphine base (in sesame oil) with dosages of 100, 200,and 400 μmol/kg. In these studies, the vehicles (saline or sesame oil) were used as controls. A paw pressure test was used to detect the antinociceptive effect of the testing drugs. Results: We found that nalbuphine HCI25, 50 and 100 μmol/kg produced a dose-related antinociceptive effect with durations of action of 1, 1, and 1.3 h, respectively. Nalbuphine base 100, 200 and 400 μmol/kg also produced a dose-related antinociceptive effect but with longer durations of action of 8, 24, and 48 h, respectively. On an equimolar basis (100 μmol/kg), nalbuphine base produced a 6-fold increase in the duration of action than did nalbuphine HCI. Conclusions: We conclude that intramuscular nalbuphine base produced a relatively longer duration of action than did intramuscular nalbuphine HCI.