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盐酸哌替啶肌内和皮下给药后在马体内的药代动力学和药效学。

Pharmacokinetics and pharmacodynamics of meperidine after intramuscular and subcutaneous administration in horses.

机构信息

Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia.

Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, Georgia.

出版信息

Vet Surg. 2021 Feb;50(2):410-417. doi: 10.1111/vsu.13545. Epub 2020 Nov 26.

Abstract

OBJECTIVE

To describe the pharmacokinetics and pharmacodynamics of meperidine after IM and subcutaneous administration in horses.

STUDY DESIGN

prospective, randomized, blinded, crossover trial.

ANIMALS

Six adult horses weighing 494 ± 33 kg.

METHODS

Treatments included meperidine 1 mg/kg IM with saline 6 mL subcutaneously, meperidine 1 mg/kg subcutaneously with saline 6 mL IM, and saline 6 mL subcutaneously and 6 mL IM, with a 7-day washout between treatments. Plasma meperidine concentrations and pharmacodynamic values (thermal and mechanical thresholds, physiological variables, fecal production) were collected at various time points for 24 hours. Accelerometry data were obtained for 8 hours to measure locomotor activity. Data were analyzed with a mixed effects model, and α was set at .05.

RESULTS

Meperidine terminal half-life (T ), maximal plasma concentrations, and time to maximal concentration were 186 ± 59 and 164 ± 56 minutes, 265.7 ± 47.2 and 243.1 ± 80.1 ng/mL at 17 ± 6, and 24 ± 13 minutes for IM at subcutaneous administration, respectively. No effect of treatment or time was observed on thermal or mechanical thresholds, heart rate, respiratory rate, locomotor activity, frequency of defecations, or fecal weight (P > .2 for all).

CONCLUSION

Maximum meperidine concentrations were achieved quickly with a short T in both treatment groups. Neither IM nor subcutaneous meperidine influenced thermal or mechanical threshold or physiological variables.

CLINICAL SIGNIFICANCE

The short half-life and lack of detectable antinociceptive effect do not support IM or subcutaneous administration meperidine at 1 mg/kg for analgesia in horses.

摘要

目的

描述马单次肌内和皮下注射哌替啶后的药代动力学和药效学。

研究设计

前瞻性、随机、双盲、交叉试验。

动物

六匹体重 494±33kg 的成年马。

方法

处理包括肌内注射 1mg/kg 哌替啶,皮下注射 6ml 生理盐水,皮下注射 1mg/kg 哌替啶,皮下和肌内各注射 6ml 生理盐水,每种处理之间有 7 天的洗脱期。在 24 小时内的不同时间点采集哌替啶的血浆浓度和药效学值(热和机械阈值、生理变量、粪便产量)。使用加速计数据测量 8 小时的运动活动。使用混合效应模型进行数据分析,α 值设为 0.05。

结果

哌替啶的终末半衰期(T )、最大血浆浓度和达峰时间分别为 186±59 和 164±56 分钟,265.7±47.2 和 243.1±80.1ng/mL,在肌内注射和皮下注射时分别为 17±6 和 24±13 分钟。治疗或时间对热或机械阈值、心率、呼吸率、运动活动、排便频率或粪便重量均无影响(所有 P > 0.2)。

结论

在两种治疗组中,哌替啶的最大浓度迅速达到,T 较短。肌内或皮下注射哌替啶 1mg/kg 均不影响热或机械阈值或生理变量。

临床意义

半衰期短且无可检测的镇痛作用不支持马单次肌内或皮下注射哌替啶 1mg/kg 用于镇痛。

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