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首页> 外文会议>IASTED International Conference Applied Simulation and Modelling July 24-26, 2000, in Banff, Alberta, Canada. >Modelling paracetamol pharmacokinetics with partially fuzzyfied compartment models
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Modelling paracetamol pharmacokinetics with partially fuzzyfied compartment models

机译：用部分模糊区室模型建模扑热息痛药代动力学

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摘要

Modelling of biological systems is often problematic. The lack of measurements and theoretical knowledge of the processes is the main problem. Limitations of theoretical knowledge have significant influence on model structure whereas the lack of measurements affects model parameter estimation procedures. The combination of both limitations can result in unreliable models. However, a lot of knowledge exists in form of various "recipes" that are also called expert knowledge, which are very awkward to implement in conventional modelling. Paracetamol is an antipiretic and analgesic drug, available as tablets, syrup and suppositories. The modelling aim was to characterise differences in bioavailability of two suppositories, fast and slow drugreleasing. Differences are supposed to occur because of different pathways of absorption in rectum for the two formulations. Each mechanism, involved in Paracetamol rectal absorption was known. However, they were not investigated systematically. The measurements were carried out on four healthy volunteers. Plasma levels of Paracetamol were measured, at the same time urine was collected and analysed for Paracetamol and its metabolites. Compartment modelling was chosen because of its transparent structural relation to the real system. The model parameters were estimated with Genetic algorithm. Partial fuzzyfication allowed successful combination of expert knowledge and measurements. Furthermore, the particular knowledge of processes involved in rectal absorption of Paracetamol was systematically included in the model and the reasons for different bioavailability of the two formulations could be elucidated.
机译：生物系统的建模通常存在问题。主要的问题是缺乏对过程的度量和理论知识。理论知识的局限性对模型结构有重大影响，而缺乏测量则影响模型参数估计程序。两种限制的结合会导致模型不可靠。但是，许多知识以各种“食谱”的形式存在，也被称为专家知识，这在常规建模中很难实现。扑热息痛是一种消炎镇痛药，有片剂，糖浆剂和栓剂。建模的目的是表征快速和缓慢释放两种栓剂的生物利用度差异。由于两种制剂在直肠的吸收途径不同，因此可能会出现差异。涉及扑热息痛直肠吸收的每种机制都是已知的。但是，尚未对其进行系统地调查。对四名健康志愿者进行了测量。测量血浆中扑热息痛的水平，同时收集尿液并分析扑热息痛及其代谢产物。选择隔室建模是因为它与实际系统具有透明的结构关系。使用遗传算法估计模型参数。部分模糊化可以使专家知识和测量成功结合。此外，模型中系统地包括了对乙酰氨基酚直肠吸收相关过程的特殊知识，并且可以阐明两种制剂生物利用度不同的原因。

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