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卡洛芬在麻醉猪体内的药代动力学:初步研究。

Pharmacokinetics of carprofen in anaesthetized pigs: a preliminary study.

机构信息

Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.

Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

出版信息

Vet Anaesth Analg. 2021 Jan;48(1):35-41. doi: 10.1016/j.vaa.2020.09.006. Epub 2020 Oct 19.

Abstract

OBJECTIVE

To investigate the pharmacokinetics of carprofen after a single intravenous (IV) dose and multiple oral doses administered to pigs undergoing electroporation of the pancreas.

STUDY DESIGN

Prospective experimental study.

ANIMALS

A group of eight female pigs weighing 31.74 ± 2.24 kg (mean ± standard deviation).

METHODS

Carprofen 4 mg kg was administered IV after placement of a central venous catheter during general anaesthesia with isoflurane. Blood samples were collected 30 seconds before and 5, 10, 20, 30 and 60 minutes and 2, 4, 6, 8, 12 and 24 hours after carprofen administration. Subsequently, the same dose of carprofen was administered orally, daily, for 6 consecutive days and blood collected at 36, 48, 60, 72, 96, 120, 144 and 168 hours after initial carprofen administration. Plasma was analysed using liquid chromatography with mass spectrometry. Standard pharmacokinetic parameters were calculated by compartmental analysis of plasma concentration-time curves. Data are presented as mean ± standard error.

RESULTS

The initial plasma concentration of IV carprofen was estimated at 54.57 ± 3.92 μg mL and decreased to 8.26 ± 1.07 μg mL 24 hours later. The plasma elimination curve showed a bi-exponential decline: a rapid distribution phase with a distribution half-life of 0.21 ± 0.03 hours and a slower elimination phase with an elimination half-life of 17.31 ± 3.78 hours. The calculated pharmacokinetic parameters were as follows: the area under the plasma concentration-time curve was 357.3 ± 16.73 μg mL hour, volume of distribution was 0.28 ± 0.07 L kg and plasma clearance rate was 0.19 ± 0.009 mL minute kg. The plasma concentration of carprofen, administered orally from days 2 to 7, varied from 9.03 ± 1.87 to 11.49 ± 2.15 μg mL.

CONCLUSIONS AND CLINICAL RELEVANCE

Carprofen can be regarded as a long-acting non-steroidal anti-inflammatory drug in pigs.

摘要

目的

研究电穿孔胰腺后单次静脉(IV)给药和多次口服给予卡洛芬后卡洛芬的药代动力学。

研究设计

前瞻性实验研究。

动物

一组 8 头重 31.74 ± 2.24 公斤(平均值 ± 标准差)的雌性猪。

方法

在异氟烷全身麻醉下放置中心静脉导管后,给予卡洛芬 4 mg kg IV。在卡洛芬给药前 30 秒和给药后 5、10、20、30 和 60 分钟以及 2、4、6、8、12 和 24 小时采集血样。随后,每天口服相同剂量的卡洛芬,连续 6 天,在初始卡洛芬给药后 36、48、60、72、96、120、144 和 168 小时采集血样。使用液质联用法分析血浆。通过对血浆浓度-时间曲线进行房室分析来计算标准药代动力学参数。数据以平均值 ± 标准误差表示。

结果

IV 卡洛芬的初始血浆浓度估计为 54.57 ± 3.92 μg mL,24 小时后降至 8.26 ± 1.07 μg mL。血浆消除曲线呈双指数下降:快速分布相半衰期为 0.21 ± 0.03 小时,较慢消除相半衰期为 17.31 ± 3.78 小时。计算的药代动力学参数如下:血浆浓度-时间曲线下面积为 357.3 ± 16.73 μg mL hour,分布容积为 0.28 ± 0.07 L kg,血浆清除率为 0.19 ± 0.009 mL minute kg。第 2 天至第 7 天口服给予卡洛芬,其血浆浓度为 9.03 ± 1.87 至 11.49 ± 2.15 μg mL。

结论和临床相关性

卡洛芬可被视为猪的长效非甾体抗炎药。

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