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综合药理学方法在药物发现和安全性评估中的无线电遥测和采血。

An integrative pharmacological approach to radio telemetry and blood sampling in pharmaceutical drug discovery and safety assessment.

机构信息

Safety Assessment US, AstraZeneca R&D Wilmington, DE 19850, USA.

出版信息

Biomed Eng Online. 2011 Jan 18;10:5. doi: 10.1186/1475-925X-10-5.

DOI:10.1186/1475-925X-10-5
PMID:21244682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3033855/
Abstract

BACKGROUND

A successful integration of the automated blood sampling (ABS) and telemetry (ABST) system is described. The new ABST system facilitates concomitant collection of physiological variables with blood and urine samples for determination of drug concentrations and other biochemical measures in the same rat without handling artifact.

METHOD

Integration was achieved by designing a 13 inch circular receiving antenna that operates as a plug-in replacement for the existing pair of DSI's orthogonal antennas which is compatible with the rotating cage and open floor design of the BASi Culex® ABS system. The circular receiving antenna's electrical configuration consists of a pair of electrically orthogonal half-toroids that reinforce reception of a dipole transmitter operating within the coil's interior while reducing both external noise pickup and interference from other adjacent dipole transmitters.

RESULTS

For validation, measured baclofen concentration (ABST vs. satellite (μM): 69.6 ± 23.8 vs. 76.6 ± 19.5, p = NS) and mean arterial pressure (ABST vs. traditional DSI telemetry (mm Hg): 150 ± 5 vs.147 ± 4, p = NS) variables were quantitatively and qualitatively similar between rats housed in the ABST system and traditional home cage approaches.

CONCLUSION

The ABST system offers unique advantages over traditional between-group study paradigms that include improved data quality and significantly reduced animal use. The superior within-group model facilitates assessment of multiple physiological and biochemical responses to test compounds in the same animal. The ABST also provides opportunities to evaluate temporal relations between parameters and to investigate anomalous outlier events because drug concentrations, physiological and biochemical measures for each animal are available for comparisons.

摘要

背景

描述了自动化血液采样(ABS)和遥测(ABST)系统的成功整合。新的 ABST 系统便于在不产生人为干扰的情况下,同时采集生理变量、血液和尿液样本,以确定同一大鼠中的药物浓度和其他生化指标。

方法

通过设计一个 13 英寸的圆形接收天线来实现整合,该天线作为现有 DSI 正交天线的插件替代品,与 BASi Culex® ABS 系统的旋转笼和开放式地板设计兼容。圆形接收天线的电气配置由一对电正交的半环组成,增强了在线圈内部工作的偶极子发射器的接收,同时减少了外部噪声拾取和来自其他相邻偶极子发射器的干扰。

结果

为了验证,在 ABST 系统中饲养的大鼠与传统的笼内方法相比,测量的巴氯芬浓度(ABST 与卫星(μM):69.6 ± 23.8 与 76.6 ± 19.5,p = NS)和平均动脉压(ABST 与传统的 DSI 遥测(mmHg):150 ± 5 与 147 ± 4,p = NS)变量在数量和质量上相似。

结论

ABST 系统提供了优于传统组间研究范式的独特优势,包括改善数据质量和显著减少动物使用。优越的组内模型促进了对同一动物中测试化合物的多种生理和生化反应的评估。ABST 还提供了评估参数之间的时间关系和调查异常异常事件的机会,因为每个动物的药物浓度、生理和生化测量值都可用于比较。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/5387c0419960/1475-925X-10-5-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/6c1a274e237c/1475-925X-10-5-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/52b4b4adf730/1475-925X-10-5-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/37ef3a5a8948/1475-925X-10-5-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/d2eb4911a0ac/1475-925X-10-5-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/5cf515d6181e/1475-925X-10-5-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/5387c0419960/1475-925X-10-5-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/6c1a274e237c/1475-925X-10-5-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/52b4b4adf730/1475-925X-10-5-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/37ef3a5a8948/1475-925X-10-5-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/d2eb4911a0ac/1475-925X-10-5-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/5cf515d6181e/1475-925X-10-5-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f68/3033855/5387c0419960/1475-925X-10-5-6.jpg

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