Objective

To describe the pharmacokinetics of ketamine following a short intravenous (IV) infusion to isoflurane-anesthetized rabbits.

Study design

Prospective experimental study.

Animals

A total of six adult healthy female New Zealand White rabbits.

Methods

Anesthesia was induced with isoflurane in oxygen. Following determination of isoflurane minimum alveolar concentration (MAC), the isoflurane concentration was reduced to 0.75 MAC and ketamine hydrochloride (5 mg kg^–1) was administered IV over 5 minutes. Blood samples were collected before and at 2, 5, 6, 7, 8, 9, 13, 17, 21, 35, 65, 125, 215 and 305 minutes after initiating the ketamine infusion. Samples were processed immediately and the plasma separated and stored at –80 °C until analyzed for ketamine and norketamine concentrations using liquid chromatography–mass spectrometry. Compartment models were fitted to the concentration–time data for ketamine and for ketamine plus norketamine using nonlinear mixed-effects (population) modeling.

Results

A three- and five-compartment model best fitted the plasma concentration–time data for ketamine and for ketamine plus norketamine, respectively. For the ketamine only model, the volume of distribution at steady state (Vss) was 3217 mL kg^–1, metabolic clearance was 88 mL minute^–1 kg^–1 and the terminal half-life was 59 minutes. For the model including both ketamine and norketamine, Vss were 3224 and 2073 mL kg^–1, total metabolic clearance was 107 and 52 mL minute^–1 kg^–1 and terminal half-lives were 52 and 55 minutes for the parent drug and its metabolite, respectively.

Conclusions and clinical relevance

This study characterized the pharmacokinetics of ketamine and norketamine in isoflurane-anesthetized New Zealand White rabbits following short IV infusion. The results obtained herein will be useful to determine ketamine infusion regimens in isoflurane-anesthetized rabbits.

中文翻译：

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向异氟烷麻醉的新西兰白兔短时间静脉输注氯胺酮后的药代动力学。

目的

为了描述氯胺酮在异氟烷麻醉的兔体内短暂静脉内输注后的药代动力学。

学习规划

前瞻性实验研究。

动物

总共六只成年健康的雌性新西兰白兔。

方法

在氧气中用异氟烷诱导麻醉。确定异氟醚最低肺泡浓度（MAC）后，异氟醚浓度降低至0.75 MAC，并在5分钟内静脉注射盐酸氯胺酮（5 mg kg ^–1）。在开始氯胺酮输注后的第2、5、6、7、8、9、13、17、21、35、65、125、215和305分钟和之前采集血液样本。立即处理样品，分离血浆并将其保存在–80°C，直到使用液相色谱-质谱法分析氯胺酮和去甲氯胺酮的浓度。使用非线性混合效应（种群）模型，针对氯胺酮以及氯胺酮和去甲氯胺酮的浓度-时间数据拟合隔室模型。

结果

三室和五室模型分别最适合氯胺酮，氯胺酮和去甲氯胺酮的血浆浓度-时间数据。对于仅使用氯胺酮的模型，稳态时的分布体积（Vss）为3217 mL kg ^–1，代谢清除率为88 mL分钟^–1 kg ^–1，最终半衰期为59分钟。对于包括氯胺酮和去甲胺酮的模型，母体药物及其代谢产物的Vss为3224和2073 mL kg ^–1，总代谢清除率为107和52 mL min ^–1 kg ^–1，终末半衰期为52和55分钟， 分别。

结论与临床意义

这项研究的特点是在短暂静脉输注后，异氟烷麻醉的新西兰白兔体内的氯胺酮和去甲氯胺酮的药代动力学。本文获得的结果将可用于确定异氟烷麻醉兔子的氯胺酮输注方案。