Clinical efficacy of buprenorphine after oral dosing in rats undergoing major surgery.

IF 1.3 4区 农林科学 Q2 VETERINARY SCIENCES Laboratory Animals Pub Date : 2024-02-01 Epub Date: 2023-09-05 DOI:10.1177/00236772231178417
Einar Sjaastad Nordén, Ioanni Veras, Prakash Yadav, Kari Løken, Hilde Dishington, Christian Thorstensen, Ivar Sjaastad, Henrik Rasmussen
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Abstract

Serum corticosterone, serum buprenorphine, body weight change, consumption of food and water and behaviour-based pain assessment were measured in catheterised and non-catheterised male Wistar rats undergoing myocardial infarct (MI) surgery under general anaesthesia following buprenorphine dosing by subcutaneous (Bup-SC, 0.05 mg/kg) and oral (Bup-O, 0.4 mg/kg) routes. Buprenorphine was dosed subcutaneously at half an hour before and 8, 16 and 24 hours after surgery (Bup-SC), orally at one hour before surgery (Bup-O1) or at one hour before and 12 hours after surgery (Bup-O2) in catheterised rats and at one hour before and 24 hours after surgery (Bup-O24) in non-catheterised rats. Serum corticosterone, body weight changes and food and water consumption were not significantly different between treatments in catheterised rats. Bup-SC resulted in rapidly decreasing serum concentrations below the clinically effective concentrations (1 ng/mL) already at two hours after the first dose. Bup-O provided significantly higher and slowly decreasing serum concentrations, at or above clinically effective concentrations, for 24 hours (Bup-O1) and 42 hours (Bup-O2) after surgery. In non-catheterised rats, body weight development and food consumption were significantly higher in Bup-O24 rats compared to Bup-SC rats. The results indicate that a SC buprenorphine dose of 0.05 mg/kg every eight hours provides long periods of serum concentrations below clinically effective levels, and that a higher dose and/or more frequent dosage are required to provide stable serum concentrations at or above clinically effective levels. A single oral buprenorphine dose of 0.4 mg/kg provides clinically effective and stable serum concentrations for 24 hours in rats after MI surgery.

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大手术大鼠口服丁丙诺啡的临床疗效。
通过皮下注射(Bup-SC,0.05 毫克/千克)和口服(Bup-O,0.4 毫克/千克)丁丙诺啡的途径,测量了在全身麻醉下接受心肌梗塞(MI)手术的导管和非导管雄性 Wistar 大鼠的血清皮质酮、血清丁丙诺啡、体重变化、食物和水消耗量以及基于行为的疼痛评估。对导管插入的大鼠,在手术前半小时和手术后 8、16 和 24 小时皮下注射丁丙诺啡(Bup-SC);对未插入导管的大鼠,在手术前一小时口服丁丙诺啡(Bup-O1)或在手术前一小时和手术后 12 小时口服丁丙诺啡(Bup-O2);对未插入导管的大鼠,在手术前一小时和手术后 24 小时口服丁丙诺啡(Bup-O24)。导尿大鼠的血清皮质酮、体重变化以及食物和水消耗量在不同处理之间没有显著差异。Bup-SC 可使血清中的皮质酮浓度迅速下降,在首次给药后两小时已低于临床有效浓度(1 纳克/毫升)。术后 24 小时(Bup-O1)和 42 小时(Bup-O2),Bup-O 可使血清浓度明显升高并缓慢下降,达到或超过临床有效浓度。与 Bup-SC 大鼠相比,未接受导管插入手术的 Bup-O24 大鼠的体重增长和食物消耗量明显更高。结果表明,每 8 小时一次 0.05 毫克/千克的丁丙诺啡皮下注射剂量可使血清浓度长期低于临床有效水平,需要更大的剂量和/或更频繁的剂量才能使血清浓度稳定在或高于临床有效水平。在心肌梗死手术后的大鼠身上,单次口服 0.4 毫克/千克的丁丙诺啡剂量可在 24 小时内提供临床有效和稳定的血清浓度。
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来源期刊
Laboratory Animals
Laboratory Animals 生物-动物学
CiteScore
4.90
自引率
8.30%
发文量
64
审稿时长
6-12 weeks
期刊介绍: The international journal of laboratory animal science and welfare, Laboratory Animals publishes peer-reviewed original papers and reviews on all aspects of the use of animals in biomedical research. The journal promotes improvements in the welfare or well-being of the animals used, it particularly focuses on research that reduces the number of animals used or which replaces animal models with in vitro alternatives.
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