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在新生仔猪和断奶仔猪中进行重复尿液和血液采样以用于药物发现中的药代动力学和药效学建模:一项初步研究。

Repetitive urine and blood sampling in neonatal and weaned piglets for pharmacokinetic and pharmacodynamic modelling in drug discovery: a pilot study.

作者信息

Gasthuys Elke, Schauvliege Stijn, van Bergen Thomas, Millecam Joske, Cerasoli Ilaria, Martens Ann, Gasthuys Frank, Vandecasteele Tim, Cornillie Pieter, Van den Broeck Wim, Boyen Filip, Croubels Siska, Devreese Mathias

机构信息

1 Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

2 Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

出版信息

Lab Anim. 2017 Oct;51(5):498-508. doi: 10.1177/0023677217692372. Epub 2017 Feb 8.

Abstract

Piglets are considered to be suitable animal models for predicting the pharmacokinetics and pharmacodynamics (PK/PD) of test drugs for potential use in the paediatric population. Such PK/PD studies require multiple blood and urine samplings. The goal of the present study was to determine a suitable blood collection strategy applicable in the youngest age categories of six days, four weeks and eight weeks of age, as well as a urine collection technique for male piglets in the same age categories. Blood was collected either by a surgically-placed jugular vein catheter (six days old [ n = 4] and four weeks old [ n = 2] piglets) or by direct venepuncture of the jugular vein (four weeks old [ n = 2] and eight weeks old [ n = 4] piglets). A non-invasive method for total volume urine collection in male piglets was also developed using a urine pouch. No specific complications were encountered during anaesthesia or surgery for jugular catheter placement. After a 24 h recovery period, urine and blood were easily collected without technical complications. One piglet was humanely killed at week 2 because of septicaemia. Histological analysis of both veins in all four piglets revealed negligible damage to the blood vessel wall. In conclusion, the presented techniques for blood (jugular catheter and direct venepuncture) and urine collection (pouches) are suitable for PK/PD studies in piglets.

摘要

仔猪被认为是预测受试药物药代动力学和药效学(PK/PD)的合适动物模型,这些药物可能用于儿科人群。此类PK/PD研究需要多次采集血液和尿液样本。本研究的目的是确定一种适用于6日龄、4周龄和8周龄最年幼年龄组的合适采血策略,以及相同年龄组雄性仔猪的尿液采集技术。血液采集方法为:通过手术放置颈静脉导管(6日龄[n = 4]和4周龄[n = 2]仔猪)或直接颈静脉穿刺(4周龄[n = 2]和8周龄[n = 4]仔猪)。还开发了一种使用尿袋的雄性仔猪总尿量非侵入性采集方法。在颈静脉导管放置的麻醉或手术过程中未遇到特殊并发症。经过24小时恢复期后,尿液和血液易于采集,且无技术并发症。1头仔猪在第2周因败血症被安乐死。对所有4头仔猪的两条静脉进行组织学分析,结果显示血管壁损伤可忽略不计。总之,所介绍的血液采集技术(颈静脉导管和直接静脉穿刺)和尿液采集技术(尿袋)适用于仔猪的PK/PD研究。

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