|
In vitro to in vivo extrapolation refers to the qualitative or quantitative transposition of experimental results or observations made in vitro to predicts phenomena in vivo, on full living organisms. The problem of transposing in vitro results is particularly acute in areas such as toxicology where animal experiments are being increasingly replaced by alternative tests. Results obtained from ''in vitro'' experiments cannot usually be transposed as is to predict the reaction of an entire organism ''in vivo''. Build a consistent and reliable extrapolation procedure from ''in vitro'' results to ''in vitro'' is therefore extremely important. Two solutions are now commonly accepted: *(1) Increasing the complexity of ''in vitro'' systems to reproduce tissues and interactions between them (as in “human on chip” systems). *(2) Using mathematical modeling to numerically simulate the behavior of the complex system, the ''in vitro'' data providing model parameter values.〔 〕 The two approaches are not incompatible: better ''in vitro'' systems will provide better data to mathematical models. On the other hand increasingly sophisticated ''in vitro'' experiments collect increasingly numerous, complex, and challenging data to integrate: Mathematical models, such as systems biology models are much needed here. IVIVE can be split in two steps: (1) dealing with pharmacokinetics (PK) and (2) dealing with pharmacodynamics (PD). Basically, PK describes quantitatively the fate of molecules in the body; PD focuses on their effects (therapeutic or toxic) at the biological target(s) level. It is classical to differentiate PK from PD, but they form a continuum and there may be feedback one on each other.() == Extrapolating pharmacokinetics == Since the timing and intensity of effects on a given target depend on the concentration time course of candidate drug (parent molecule or metabolites) at that target site, in vivo tissue and organ sensitivities can be completely different or even inverse of those observed on cells cultured and exposed ''in vitro''. That indicates that extrapolating effects observed in vitro needs a quantitative model of in vivo PK. It is generally accepted that physiologically based PK (PBPK) models are central to the extrapolations. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「In vitro to in vivo extrapolation」の詳細全文を読む スポンサード リンク
|