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⁻¹ 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⁻¹ and decreased to 8.26 ± 1.07 μg mL⁻¹ 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⁻¹ hour, volume of distribution was 0.28 ± 0.07 L kg⁻¹ and plasma clearance rate was 0.19 ± 0.009 mL minute⁻¹ kg⁻¹. 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⁻¹.

Conclusions and clinical relevance

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

中文翻译：

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卡洛芬在麻醉猪体内的药代动力学：初步研究

客观的

研究单次静脉注射 (IV) 剂量和多次口服给药后，卡洛芬对进行胰腺电穿孔的猪的药代动力学。

学习规划

前瞻性实验研究。

动物

一组八头​​母猪，体重为 31.74 ± 2.24 kg（平均值 ± 标准偏差）。

方法

在异氟醚全身麻醉期间放置中心静脉导管后，静脉内给予卡洛芬4 mg kg ^-1。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，连续 6 天每天口服相同剂量的卡洛芬，并在初始卡洛芬给药后 36、48、60、72、96、120、144 和 168 小时收集血液。使用液相色谱和质谱分析血浆。通过血浆浓度-时间曲线的区室分析计算标准药代动力学参数。数据表示为平均值±标准误差。

结果

IV carprofen 的初始血浆浓度估计为 54.57 ± 3.92 μg mL ^-1并在24 小时后降低至 8.26 ± 1.07 μg mL ^-1。血浆消除曲线呈双指数下降：分布半衰期为 0.21 ± 0.03 小时的快速分布期和消除半衰期为 17.31 ± 3.78 小时的较慢消除期。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 ^-1小时，分布容积为 0.28 ± 0.07 L kg ^-1，血浆清除率为 0.19 ± 0.009 mL min ^-1公斤^-1. 从第 2 天到第 7 天口服给药的卡洛芬血浆浓度在 9.03 ± 1.87 至 11.49 ± 2.15 μg mL ^{-1 之间变化}。

结论和临床相关性

卡洛芬可视为猪的长效非甾体抗炎药。