* 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.
=>1.〜に慣れて, 2.用いられた, 中古の
Overview of verb use
The verb use has 6 senses (first 3 from tagged texts)
1. (603) use, utilize, utilise, apply, employ -- (put into service; make work or employ for a
particular purpose or for its inherent or natural purpose; "use your head!"; "we only use Spanish at
home"; "I can't use this tool"; "Apply a magnetic field here"; "This thinking was applied to many
projects"; "How do you utilize this tool?"; "I apply this rule to get good results"; "use the
plastic bags to store the food"; "He doesn't know how to use a computer")
2. (12) use, habituate -- (take or consume (regularly or habitually); "She uses drugs rarely")
3. (8) use, expend -- (use up, consume fully; "The legislature expended its time on school
questions")
4. use -- (seek or achieve an end by using to one's advantage; "She uses her influential friends to
get jobs"; "The president's wife used her good connections")
5. practice, apply, use -- (avail oneself to; "apply a principle"; "practice a religion"; "use care
when going down the stairs"; "use your common sense"; "practice non-violent resistance")
6. use -- (habitually do something (use only in the past tense); "She used to call her mother every
week but now she calls only occasionally"; "I used to get sick when I ate in that dining hall";
"They used to vacation in the Bahamas")
Overview of adj used
The adj used has 3 senses (first 3 from tagged texts)
1. (4) used -- (employed in accomplishing something; "the principle of surprise is the most used and
misused of all the principles of war"- H.H.Arnold & I.C.Eaker)
2. (1) exploited, ill-used, put-upon, used, victimized, victimised -- (of persons; taken advantage
of; "after going out of his way to help his friend get the job he felt not appreciated but used")
3. (1) secondhand, used -- (previously used or owned by another; "bought a secondhand (or used)
car")
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