Department of Safety Pharmacology, Abbvie, North Chicago, Illinois;, Email:
Department of Safety Pharmacology, Abbvie, North Chicago, Illinois.
Comp Med. 2021 Apr 1;71(2):133-140. doi: 10.30802/AALAS-CM-20-000083. Epub 2021 Apr 4.
Successful implementation of automated blood sampling (ABS) into a telemetry instrumented canine cardiovascular model provides simultaneous cardiovascular assessment of novel compounds while collecting multiple blood samples for analysis of drug level, cytokines, and biomarkers. Purpose-bred male Beagle dogs ( = 36) were instrumented with a dual-pressure telemetry transmitter and vascular access port. Modifications to acclimation practices, surgical procedures, and housing were required for implementation of ABS in our established cardiovascular canine telemetry colony. These modifications have increased the use and reproducibility of the model by combining early pharmacokinetic and cardiovascular studies, thus achieving both refinement and reduction from a 3R perspective. In addition, the modified model can shorten timelines and reduce the compound requirement in early stages of drug development. This telemetry-ABS model provides an efficient means to quickly identify potential effects on key cardiovascular parameters in a large animal species and to obtain a more complete pharmacokinetic-pharmacodynamic profile for discovery compounds.
成功将自动化采血（ABS）应用于遥测仪器化犬心血管模型中，为新型化合物提供了同时进行心血管评估的机会，同时采集多个血液样本以分析药物水平、细胞因子和生物标志物。经过选育的雄性比格犬（=36 只）被植入了双压遥测发射器和血管接入端口。为了在我们现有的心血管犬遥测群体中实施 ABS，需要对适应实践、手术程序和饲养进行修改。这些修改通过将早期药代动力学和心血管研究结合起来，增加了模型的使用和可重复性，从而从 3R 的角度实现了改进和减少。此外，改良后的模型可以缩短时间线并减少药物开发早期阶段的化合物需求。这种遥测-ABS 模型提供了一种有效的方法，可以快速识别在大型动物物种中关键心血管参数的潜在影响，并为发现化合物获得更完整的药代动力学-药效学特征。
