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首页> 外文期刊>The Journal of Antimicrobial Chemotherapy >Development of an integrated semi-automated system for in vitro pharmacodynamic modelling.
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Development of an integrated semi-automated system for in vitro pharmacodynamic modelling.

机译：开发用于体外药效学建模的集成半自动化系统。

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OBJECTIVES: The aim of this study was to develop an integrated system for in vitro pharmacodynamic modelling of antimicrobials with greater flexibility, easier control and better accuracy than existing in vitro models. METHODS: Custom-made bottle caps, fittings, valve controllers and a modified bench-top shaking incubator were used. A temperature-controlled automated sample collector was built. Computer software was developed to manage experiments and to control the entire system including solenoid pinch valves, peristaltic pumps and the sample collector. The system was validated by pharmacokinetic simulations of linezolid 600 mg infusion. The antibacterial effect of linezolid against multiple Staphylococcus aureus strains was also studied in this system. RESULTS: An integrated semi-automated bench-top system was built and validated. The temperature-controlled automated sample collector allowed unattended collection and temporary storage of samples. The system software reduced the labour necessary for many tasks and also improved the timing accuracy for performing simultaneous actions in multiple parallel experiments. The system was able to simulate human pharmacokinetics of linezolid 600 mg intravenous infusion accurately. A pharmacodynamic study of linezolid against multiple S. aureus strains with a range of MICs showed that the required 24 h free drug AUC/MIC ratio was approximately 30 in order to keep the organism counts at the same level as their initial inoculum and was about > or = 68 in order to achieve > 2 log(10) cfu/mL reduction in the in vitro model. CONCLUSIONS: The integrated semi-automated bench-top system provided the ability to overcome many of the drawbacks of existing in vitro models. It can be used for various simple or complicated pharmacokinetic/pharmacodynamic studies efficiently and conveniently.
机译：目的：本研究的目的是开发一个集成系统，用于比现有的体外模型具有更大的灵活性，更容易控制和更高的准确性，从而对抗菌药物进行体外药效学建模。方法：使用定制的瓶盖，配件，阀门控制器和改进的台式摇动培养箱。建立了温度控制的自动样品收集器。开发了计算机软件来管理实验并控制整个系统，包括电磁夹管阀，蠕动泵和样品收集器。通过利奈唑胺600 mg输注的药代动力学模拟验证了该系统。在该系统中还研究了利奈唑胺对多种金黄色葡萄球菌菌株的抗菌作用。结果：构建并验证了集成的半自动台式系统。温度控制的自动样品收集器允许无人值守收集和临时存储样品。系统软件减少了许多任务所需的工作量，还提高了在多个并行实验中执行同时动作的定时精度。该系统能够准确模拟利奈唑胺600 mg静脉输注的人体药代动力学。利奈唑胺对多种MIC范围内的多种金黄色葡萄球菌菌株的药效学研究表明，所需的24小时游离药物AUC / MIC比约为30，以使生物体计数与其初始接种物保持在同一水平，且约为>或= 68，以在体外模型中降低> 2 log（10）cfu / mL。结论：集成的半自动台式系统提供了克服现有体外模型的许多缺点的能力。它可以有效，方便地用于各种简单或复杂的药代动力学/药效学研究。

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