Department of Biomedical Engineering, College of Automation Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China.
Engineering College, China Pharmaceutical University, Nanjing, 211198, China.
Mol Imaging Biol. 2024 Feb;26(1):138-147. doi: 10.1007/s11307-023-01883-w. Epub 2023 Dec 19.
The data acquisition of drug metabolism analysis requires a lot of time and animal resources. However, there are often many deviations in the results of pharmacokinetic analysis. Conventional methods cannot measure the blood drug concentration data in multiple tissues at the same time, and the data is obtained by in vitro measurement, which produces time errors, in vitro data errors, and individual differences between animals. In the analysis of pharmacokinetic parameters, it will seriously affect the pass rate of clinical trials of R&D drugs and the accuracy of the dosing schedule. To the best of our knowledge, we have not found the study of in vivo blood drug concentration using multi-channel equipment. Therefore, the purpose of this paper is to build a set of multi-organ monitoring and analysis instruments for synchronously monitoring the metabolism of drugs in various tissues of small animals, so as to obtain real in vivo data of blood drug concentration in real time.
Using the fluorescence properties and laser-induced fluorescence principle of drugs, we designed six channels to monitor the changes of fluorescence-labeled drugs in their main metabolic organs, a multi-channel calibration method was proposed to improve the accuracy of the time-division multiplexing, the real-time collection of drug concentration in vivo is realized, and the drug metabolism curve in vivo can be observed.
The instrument satisfies the collection of small doses of drugs such as microgram; the detection sensitivity can reach 10 ng/ml, and can monitor and collect the drug metabolism of multiple small animal tissues at the same time, which greatly reduces the use of animals, reduces the differences between individuals, and reduces consumption cost and improve the detection efficiency of parameters, and obtain data information that is closer to the real biology.
The real-time continuous monitoring and data collection of the drug metabolism in the plasma of living small animals and the important organs such as kidney, liver, and spleen were realized. The research and development of new drugs and clinical research have higher practical value.
药物代谢分析的数据采集需要大量的时间和动物资源。然而,药代动力学分析的结果往往存在许多偏差。传统方法无法同时测量多个组织中的血液药物浓度数据,并且数据是通过体外测量获得的,这会产生时间误差、体外数据误差和动物个体差异。在药代动力学参数分析中,会严重影响研发药物临床试验的通过率和给药方案的准确性。据我们所知,尚未发现使用多通道设备进行体内血液药物浓度研究。因此,本文的目的是构建一套用于同步监测小动物各组织中药物代谢的多器官监测与分析仪器,以实时获得真实的体内血液药物浓度数据。
利用药物的荧光特性和激光诱导荧光原理,我们设计了六个通道来监测荧光标记药物在其主要代谢器官中的变化,提出了一种多通道校准方法来提高时分复用的准确性,实现了体内药物浓度的实时采集,并观察体内药物代谢曲线。
该仪器满足微克级等小剂量药物的采集;检测灵敏度可达 10ng/ml,可同时监测和采集多个小动物组织的药物代谢情况,大大减少了动物的使用量,降低了个体差异,降低了消耗成本,提高了参数检测效率,并获得更接近真实生物学的数据信息。
实现了活体小动物血浆及肾、肝、脾等重要器官中药物代谢的实时连续监测和数据采集。对新药研发和临床研究具有较高的实用价值。