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皮下给予氯胺酮通过 Omnipod®系统在狗的药代动力学。

Pharmacokinetics of subcutaneous ketamine administration via the Omnipod® system in dogs.

机构信息

College of Veterinary Medicine, NC State University, Raleigh, North Carolina, USA.

Duke University School of Medicine, Durham, North Carolina, USA.

出版信息

J Vet Pharmacol Ther. 2024 Jul;47(4):353-358. doi: 10.1111/jvp.13440. Epub 2024 Mar 27.

DOI:10.1111/jvp.13440
PMID:38536664
Abstract

Ketamine is an injectable anesthetic agent with analgesic and antidepressant effects that can prevent maladaptive pain. Ketamine is metabolized by the liver into norketamine, an active metabolite. Prior rodent studies have suggested that norketamine is thought to contribute up to 30% of ketamine's analgesic effect. Ketamine is usually administered as an intravenous (IV) bolus injection or continuous rate infusion (CRI) but can be administered subcutaneously (SC) and intramuscularly (IM). The Omnipod® is a wireless, subcutaneous insulin delivery device that adheres to the skin and delivers insulin as an SC CRI. The Omnipod® was used in dogs for postoperative administration of ketamine as a 1 mg/kg infusion bolus (IB) over 1 hour (h). Pharmacokinetics (PK) showed plasma ketamine concentrations between 42 and 326.1 ng/mL. The median peak plasma concentration was 79.5 (41.9-326.1) ng/mL with a Tmax of 60 (30-75) min. After the same infusion bolus, the corresponding norketamine PK showed plasma drug concentrations between 22.0 and 64.8 ng/mL. The median peak plasma concentration was 43.0 (26.1-71.8) ng/mL with a median Tmax of 75 min. The median peak ketamine plasma concentration exceeded 100 ng/mL in dogs for less than 1 h post infusion. The Omnipod® system successfully delivered subcutaneous ketamine to dogs in the postoperatively.

摘要

氯胺酮是一种注射用麻醉剂,具有镇痛和抗抑郁作用,可以预防适应性疼痛。氯胺酮在肝脏中代谢为去甲氯胺酮,一种活性代谢物。先前的啮齿动物研究表明,去甲氯胺酮被认为对氯胺酮的镇痛作用贡献高达 30%。氯胺酮通常作为静脉内(IV)推注或持续速率输注(CRI)给药,但也可以皮下(SC)和肌肉内(IM)给药。 Omnipod®是一种无线、皮下胰岛素输送装置,它附着在皮肤上并以 SC CRI 的形式输送胰岛素。 Omnipod®曾用于狗的术后给予氯胺酮,剂量为 1mg/kg 输注推注(IB),持续 1 小时(h)。药代动力学(PK)显示血浆氯胺酮浓度在 42 至 326.1ng/mL 之间。中位血浆峰浓度为 79.5(41.9-326.1)ng/mL,Tmax 为 60(30-75)分钟。在相同的输注推注后,相应的去甲氯胺酮 PK 显示血浆药物浓度在 22.0 和 64.8ng/mL 之间。中位血浆峰浓度为 43.0(26.1-71.8)ng/mL,中位 Tmax 为 75 分钟。在输注后,狗的中位血浆氯胺酮峰浓度超过 100ng/mL 的时间不到 1 小时。 Omnipod®系统成功地向术后的狗输送了皮下氯胺酮。

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