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猪(家猪)体内透皮芬太尼和丁丙诺啡的血浆浓度。

Plasma concentrations of transdermal fentanyl and buprenorphine in pigs (Sus scrofa domesticus).

作者信息

Osorio Lujan Suzanne, Habre Walid, Daali Youssef, Pan Zhaoxin, Kronen Peter W

机构信息

Heart Institute, Department of Pediatrics, Children's Hospital Colorado & University of Colorado, Aurora, CO, USA.

Unit for Anaesthesiological Investigations, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.

出版信息

Vet Anaesth Analg. 2017 May;44(3):665-675. doi: 10.1016/j.vaa.2016.09.002. Epub 2017 Jan 11.

Abstract

OBJECTIVE

To determine the absorption characteristics of fentanyl and buprenorphine administered transdermally in swine.

STUDY DESIGN

A randomized comparative experimental trial.

ANIMALS

Twenty-four Yorkshire gilts weighing 27.8±2.2 kg (mean±standard deviation).

METHODS

Animals were randomly assigned to different doses of transdermal patches (TPs) of fentanyl (50 μg hour, 75 μg hour and 100 μg hour) or buprenorphine (35 μg hour and 70 μg hour), once or twice. Thirteen blood samples were obtained for each TP applied. Plasma concentrations were determined, and the area under the curve, peak serum concentration (C) and time to C were calculated.

RESULTS

Fentanyl: C was observed at different time points: for the first TP application: 30 hours for 50 μg hour, 6 hours for 75 μg hour and 100 μg hour patches; and for the second TP application: 30 hours for 50 μg hour and 36 hours for 75 μg hour patches. Buprenorphine: serum concentrations were not detected for the 35 μg hour patch; C was observed at different times for the 70 μg hour patch: 18 hours (n = 1), 24 hours (n = 3), 30 hours (n = 1) and 42 hours (n = 1) after application of the first patch and 12 hours after the second patch.

CONCLUSIONS AND CLINICAL RELEVANCE

A relevant serum concentration obtained with fentanyl TP dosed at 75 μg hour or 100 μg hoursuggests that TPs could represent an analgesia option for laboratory pigs weighing 25-30 kg. As concentrations of buprenorphine were variable, this study does not support the use of buprenorphine TPs in pigs. Consecutive fentanyl or buprenorphine TPs did not provide reliable serum concentrations. Further pharmacokinetic studies and analgesiometric tests in swine are needed to confirm the clinical adequacy of TPs.

摘要

目的

确定猪经皮给予芬太尼和丁丙诺啡的吸收特性。

研究设计

一项随机对照试验。

动物

24头体重27.8±2.2千克(均值±标准差)的约克夏母猪。

方法

将动物随机分为不同剂量的芬太尼(50微克/小时、75微克/小时和100微克/小时)或丁丙诺啡(35微克/小时和70微克/小时)透皮贴剂(TPs)组,给药一次或两次。每贴用一种TPs后采集13份血样。测定血浆浓度,并计算曲线下面积、血清峰值浓度(C)和达峰时间。

结果

芬太尼:在不同时间点观察到C:首次使用TPs时,50微克/小时的贴剂为30小时,75微克/小时和100微克/小时的贴剂为6小时;第二次使用TPs时,50微克/小时的贴剂为30小时,75微克/小时的贴剂为36小时。丁丙诺啡:35微克/小时的贴剂未检测到血清浓度;70微克/小时的贴剂在不同时间观察到C:首次贴用后18小时(n = 1)、24小时(n = 3)、30小时(n = 1)和42小时(n = 1),第二次贴用后12小时。

结论及临床意义

75微克/小时或100微克/小时剂量的芬太尼TPs可获得相关血清浓度,提示TPs可为体重25 - 30千克的实验猪提供一种镇痛选择。由于丁丙诺啡浓度存在差异,本研究不支持在猪中使用丁丙诺啡TPs。连续使用芬太尼或丁丙诺啡TPs无法提供可靠的血清浓度。需要在猪中进行进一步的药代动力学研究和镇痛测试,以确认TPs的临床适用性。

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