F344 大鼠肌肉注射氯胺酮后的药代动力学。,Drug Testing and Analysis

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F344 大鼠肌肉注射氯胺酮后的药代动力学。
Drug Testing and Analysis ( IF 2.6 ) Pub Date : 2018-08-14 , DOI: 10.1002/dta.2468
Benjamin Moeller _{1,

2} , Brenna Espelien ₁ , Waylon Weber ₁ , Philip Kuehl ₁ , Melanie Doyle-Eisele ₁ , C Edwin Garner ₁ , Jacob D McDonald ₁ , Efrain Garcia ₃ , Robert Raulli ₃ , Judith Laney ₃

Affiliation

氯胺酮是一种谷氨酸 N-甲基-D-天冬氨酸受体拮抗剂，是一种速效解离麻醉剂。它已被提议与其他药物（阿托品、咪达唑仑、解磷定）一起作为当前有机磷和神经毒剂暴露护理标准 (SOC) 中使用的辅助治疗。氯胺酮是一种药剂，大多数急诊科临床医生都可以使用，并且具有广泛的治疗指数，对人类的作用具有良好的特征。本研究的目的是确定 F344 大鼠单次或重复肌肉注射亚麻醉水平（7.5 mg/kg 或 30 mg/kg）氯胺酮（有或没有 SOC）后氯胺酮及其活性代谢物去甲氯胺酮的药代动力学特征。给药后，收集血浆和脑组织，并使用液相色谱-质谱法进行分析，以定量氯胺酮和去甲氯胺酮。样品分析后，使用非房室分析确定药代动力学。添加当前 SOC 对肌内给药后氯胺酮的药代动力学影响极小，每 90 分钟重复给药 7.5 mg/kg 可使血浆浓度持续高于 100 ng/mL。含有和不含 SOC 的氯胺酮在大鼠体内的药代动力学支持进一步研究动物模型暴露神经毒剂后氯胺酮与 SOC 联合给药的功效。

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The pharmacokinetics of ketamine following intramuscular injection to F344 rats.

Ketamine is a glutamate N‐methyl‐D‐aspartate receptor antagonist that is a rapid‐acting dissociative anesthetic. It has been proposed as an adjuvant treatment along with other drugs (atropine, midazolam, pralidoxime) used in the current standard of care (SOC) for organophosphate and nerve agent exposures. Ketamine is a pharmaceutical agent that is readily available to most clinicians in emergency departments and possesses a broad therapeutic index with well‐characterized effects in humans. The objective of this study was to determine the pharmacokinetic profile of ketamine and its active metabolite, norketamine, in F344 rats following single or repeated intramuscular administrations of subanesthetic levels (7.5 mg/kg or 30 mg/kg) of ketamine with or without the SOC. Following administration, plasma and brain tissues were collected and analyzed using a liquid chromatography–mass spectrometry method to quantitate ketamine and norketamine. Following sample analysis, the pharmacokinetics were determined using non‐compartmental analysis. The addition of the current SOC had a minimal impact on the pharmacokinetics of ketamine following intramuscular administration and repeated dosing at 7.5 mg/kg every 90 minutes allows for sustained plasma concentrations above 100 ng/mL. The pharmacokinetics of ketamine with and without the SOC in rats supports further investigation of the efficacy of ketamine co‐administration with the SOC following nerve agent exposure in animal models.

更新日期：2018-08-14

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