- 學位論文
評估單一劑量Sebacoyl Dinalbulphine Ester肌肉注射在犬隻子宮卵巢切除術術後疼痛控制之安全性、效力與藥物動力學: 隨機、觀察者盲性與使用活性對照組之研究
Safety, Efficacy and Pharmacokinetics of Single Dose Intramuscular Sebacoyl Dinalbulphine Ester for Dogs in Post-Ovariohysterectomy Pain management: A Randomized, Observer Blinded, and Active Control Study
摘要
鴉片類藥物常用於術後疼痛控制中，而嗎啡(morphine)是最常使用之標準鴉片類止痛藥。然而，使用嗎啡時也需要考量鴉片類藥物相關之副作用與其相對較短的半衰期。Nalbuphine是一種kappa-受器致效劑與部分mu-受器拮抗劑，在提供相當止痛效果的同時，也可以降低嗎啡相關的副作用。Sebacoyl dinalbulphine ester (SDE)則是一種以nalbuphine與diester合成的前驅藥物，因為具有高脂溶性的特性，因此可以延長nalbuphine在肌肉注射時的作用時間。本實驗為一篇隨機、觀察者盲性、使用活性對照組的研究，以評估單一肌肉注射SDE在犬隻子宮卵巢切除術術後疼痛控制中的安全性、效力與藥物動力學。實驗共納入32隻安排進行子宮卵巢切除術之犬隻，並將其隨機分為三個治療組別(meloxicam 0.1 mg/kg, SDE15 mg/kg and SDE 30 mg/kg)，以Canine acute pain scale (CAPS)和 short form of the Glasgow composite pain scale (GCPS)評估其術後疼痛程度，並記錄任何不良反應。 實驗結果顯示，三個治療組別間在各個時間點的CAPS與GCPS評分皆沒有顯著差異。而儘管沒有顯著差異，但高劑量SDE組擁有相對較好的疼痛控制，其代表SDE造成的止痛效果可能具有劑量依賴性的特性。在低劑量SDE與高劑量SDE組中，沒有任何犬隻在手術後24小時內需要給予救援止痛藥。實驗中沒有觀察到任何嚴重的不良反應。在三個治療組別中，過度流涎與噁心(28.1%)是最常見藥物相關的不良反應。在高劑量SDE組別中，有一個實驗病患(8.3 %)在給藥後2小時出現了注射部位反應，但在術後24小時後自行緩解。總結而言，在適當的劑量下，SDE可以在犬隻子宮卵巢切除術術後提供良好的止痛，並擁有良好的耐受性。
並列摘要
Opioids are commonly used in postoperative pain management and morphine is the mostly used and standard opioid analgesic drug. However, opioid related adverse effects and relative short elimination half life should be concerned. Nalbuphine, a potent kappa-receptor agonist and partial mu-receptor antagonist, could reduce the risk of adverse effect associated with morphine and provide comparable analgesic effect. Sebacoyl dinalbulphine ester (SDE) is a synthetic diester prodrug of nalbuphine which has high lipophilicity that prolongs the duration of nalbuphine after intramuscular (IM) injection. A randomized, observer blinded, single dose, active-controlled study was performed to evaluate the safety, efficacy and pharmacokinetics of IM SDE for dogs in post-ovariohysterectomy pain management. Thirty-two dogs scheduled for ovariohysterectomy were enrolled and randomized into 3 treatment groups (meloxicam 0.1 mg/kg, SDE15 mg/kg and SDE 30 mg/kg). Canine acute pain scale (CAPS) and short form of the Glasgow composite pain scale (GCPS) were used to assess postoperative pain. Any adverse events were recorded. The results revealed that there was no significant difference of CAPS and GCPS between the 3 treatment groups at any time point. High dose SDE group yielded better pain control than low dose SDE and indicated that the analgesia provided by SDE is dose-dependent. No dogs in either low or high dose SDE required rescue analgesic in first 24 hours post-operatively. No serious adverse event was reported. Hypersalivation and nausea (28.1%) was the most common drug-related adverse event among the 3 treatment groups. Only 1 dog (8.3%) in high dose SDE had mild muscle swelling at the injection site and resolved spontaneously after 24 hours post-operatively. In conclusion, SDE is generally well-tolerated and a fine analgesic for pain management during the first 24 hours in dogs following ovariohysterectomy by using an adequate dose.
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