* Combining the 'bottom up' and 'top down' approaches in pharmacokinetic modelling: fitting PBPK models to observed clinical data.
- Pharmacokinetic models range from being entirely exploratory and empirical, to semi-mechanistic and ultimately complex physiologically based pharmacokinetic (PBPK) models. This choice is conditional on the modelling purpose as well as the amount and quality of the available data. The main advantage of PBPK models is that they can be used to extrapolate outside the studied population and experimental conditions. The trade-off for this advantage is a complex system of differential equations with a considerable number of model parameters. When these parameters cannot be informed from in vitro or in silico experiments they are usually optimized with respect to observed clinical data. Parameter estimation in complex models is a challenging task associated with many methodological issues which are discussed here with specific recommendations. Concepts such as structural and practical identifiability are described with regards to PBPK modelling and the value of experimental design and sensitivity analyses is sketched out. Parameter estimation approaches are discussed, while we also highlight the importance of not neglecting the covariance structure between model parameters and the uncertainty and population variability that is associated with them. Finally the possibility of using model order reduction techniques and minimal semi-mechanistic models that retain the physiological-mechanistic nature only in the parts of the model which are relevant to the desired modelling purpose is emphasized. Careful attention to all the above issues allows us to integrate successfully information from in vitro or in silico experiments together with information deriving from observed clinical data and develop mechanistically sound models with clinical relevance.
=>制度組織体系的方式, システム, 組織, 整然とした手順, (思想などの)体系, 体制
Overview of noun system
The noun system has 9 senses (first 8 from tagged texts)
1. (43) system -- (instrumentality that combines interrelated interacting artifacts designed to work
as a coherent entity; "he bought a new stereo system"; "the system consists of a motor and a small
computer")
2. (23) system, scheme -- (a group of independent but interrelated elements comprising a unified
whole; "a vast system of production and distribution and consumption keep the country going")
3. (14) system -- ((physical chemistry) a sample of matter in which substances in different phases
are in equilibrium; "in a static system oil cannot be replaced by water on a surface"; "a system
generating hydrogen peroxide")
4. (10) system, system of rules -- (a complex of methods or rules governing behavior; "they have to
operate under a system they oppose"; "that language has a complex system for indicating gender")
5. (8) arrangement, organization, organisation, system -- (an organized structure for arranging or
classifying; "he changed the arrangement of the topics"; "the facts were familiar but it was in the
organization of them that he was original"; "he tried to understand their system of classification")
6. (7) system -- (a group of physiologically or anatomically related organs or parts; "the body has
a system of organs for digestion")
7. (6) system -- (a procedure or process for obtaining an objective; "they had to devise a system
that did not depend on cooperation")
8. (1) system -- (the living body considered as made up of interdependent components forming a
unified whole; "exercise helped him get the alcohol out of his system")
9. organization, organisation, system -- (an ordered manner; orderliness by virtue of being
methodical and well organized; "his compulsive organization was not an endearing quality"; "we can't
do it unless we establish some system around here")
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