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单次肌肉注射后酮咯酸在野生东部箱龟(卡罗莱纳箱龟指名亚种)体内的药代动力学

Pharmacokinetics of ketorolac in wild Eastern box turtles (Terrapene carolina carolina) after single intramuscular administration.

作者信息

Cerreta Anthony J, Masterson Chris A, Lewbart Gregory A, Dise Delta R, Papich Mark G

机构信息

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.

Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.

出版信息

J Vet Pharmacol Ther. 2019 Mar;42(2):154-159. doi: 10.1111/jvp.12733. Epub 2018 Nov 4.

DOI:10.1111/jvp.12733
PMID:30393871
Abstract

Ketorolac is a nonsteroidal anti-inflammatory drug that possesses potent analgesic activity comparable to morphine. The opioid shortage in the United States has led to an unreliable supply of opioids for use in rehabilitation facilities, thus underscoring the need for research on the safe and effective use of nonopioid alternatives. The goal of this study was to determine the pharmacokinetics of ketorolac after a single 0.25 mg/kg intramuscular injection administered to injured Eastern box turtles (Terrapene carolina carolina). A sparse blood sampling protocol was used to collect samples from 32 wild turtles that presented to the Turtle Rescue Team at North Carolina State University for traumatic injuries. Blood was collected from 0 to 24 hr after injection and analyzed via high-pressure liquid chromatography (HPLC). A nonlinear mixed-effects (NLME) model was fitted to the data to obtain typical values for population parameters. Using this approach, we identified a long half-life (T ) of 9.78 hr and a volume of distribution (V ) of 0.26 L/kg. We have concluded that this long T for a dose of 0.25 mg/kg ketorolac-injected IM provides plasma levels above a previously published target level for 24-hour analgesia to allow for once daily dosing.

摘要

酮咯酸是一种非甾体抗炎药,具有与吗啡相当的强效镇痛活性。美国的阿片类药物短缺导致康复机构中阿片类药物的供应不可靠,因此凸显了对非阿片类替代药物安全有效使用进行研究的必要性。本研究的目的是确定对受伤的东部箱龟(卡罗莱纳箱龟指名亚种)单次肌内注射0.25 mg/kg酮咯酸后的药代动力学。采用稀疏采血方案,从32只因外伤前来北卡罗来纳州立大学海龟救援队的野生海龟中采集样本。在注射后0至24小时采集血液,并通过高压液相色谱法(HPLC)进行分析。对数据拟合非线性混合效应(NLME)模型,以获得总体参数的典型值。使用这种方法,我们确定了9.78小时的长半衰期(T)和0.26 L/kg的分布容积(V)。我们得出结论,对于肌内注射0.25 mg/kg酮咯酸的剂量,这种长半衰期可使血浆水平在先前公布的24小时镇痛目标水平之上,从而允许每日给药一次。

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