Editing In vitro (section)

== ''In vitro'' to ''in vivo'' extrapolation ==
{{Main|In vitro to in vivo extrapolation}}
Results obtained from ''in vitro'' experiments cannot usually be transposed, as is, to predict the reaction of an entire organism ''in vivo''. Building a consistent and reliable extrapolation procedure from ''in vitro'' results to ''in vivo'' is therefore extremely important. Solutions include:

*Increasing the complexity of ''in vitro'' systems to reproduce tissues and interactions between them (as in "human on chip" systems)<ref>{{cite journal|last1=Sung|first1=JH|last2=Esch|first2=MB|last3=Shuler|first3=ML|title=Integration of in silico and in vitro platforms for pharmacokinetic-pharmacodynamic modeling|journal=Expert Opinion on Drug Metabolism & Toxicology|date=2010|volume=6|issue=9|pages=1063–1081|doi=10.1517/17425255.2010.496251|pmid=20540627|s2cid=30583735}}</ref>
*Using mathematical modeling to numerically simulate the behavior of the complex system, where the ''in vitro'' data provide model parameter values<ref>
{{cite journal
|last1=Quignot
|first1=Nadia
|last2=Bois
|first2=Frédéric Yves
|title=A computational model to predict rat ovarian steroid secretion from in vitro experiments with endocrine disruptors
|journal=PLOS ONE
|date=2013
|volume=8
|issue=1
|page=e53891
|doi=10.1371/journal.pone.0053891
|pmid=23326527
|pmc=3543310|bibcode=2013PLoSO...853891Q
|doi-access=free
}}</ref>

These two approaches are not incompatible; better ''in vitro'' systems provide better data to mathematical models. However, 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.<ref>{{Cite journal |last1=Proença |first1=Susana |last2=Escher |first2=Beate I. |last3=Fischer |first3=Fabian C. |last4=Fisher |first4=Ciarán |last5=Grégoire |first5=Sébastien |last6=Hewitt |first6=Nicky J. |last7=Nicol |first7=Beate |last8=Paini |first8=Alicia |last9=Kramer |first9=Nynke I. |date=2021-06-01 |title=Effective exposure of chemicals in in vitro cell systems: A review of chemical distribution models |journal=Toxicology in Vitro |language=en |volume=73 |pages=105133 |doi=10.1016/j.tiv.2021.105133 |pmid=33662518 |s2cid=232122825 |issn=0887-2333|doi-access=free |bibcode=2021ToxVi..7305133P }}</ref>

=== Extrapolating in pharmacology ===
In pharmacology, IVIVE can be used to approximate [[pharmacokinetics]] (PK) or [[pharmacodynamics]] (PD).<ref>{{cite journal |last1=Yadav |first1=Jaydeep |title=Recent developments in in vitro and in vivo models for improved translation of preclinical pharmacokinetic and pharmacodynamics data |journal=Drug Metab Rev |date=2021 |volume=53 |issue= 2 |pages=207-233 |doi=10.1080/03602532.2021.1922435 |pmc=8381685 }}</ref> 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. Physiologically based PK ([[PBPK]]) models are generally accepted to be central to the extrapolations.<ref>{{cite journal
|vauthors=Yoon M, Campbell JL, Andersen ME, Clewell HJ |title=Quantitative in vitro to in vivo extrapolation of cell-based toxicity assay results
|journal=Critical Reviews in Toxicology
|date=2012
|volume=42
|issue=8
|pages=633–652
|doi=10.3109/10408444.2012.692115|pmid=22667820
|s2cid=3083574
}}</ref>

In the case of early effects or those without intercellular communications, the same cellular exposure concentration  is assumed to cause the same effects, both qualitatively and quantitatively, ''in vitro'' and ''[[in vivo]]''. In these conditions, developing a simple PD model of the [[dose–response relationship]] observed ''in vitro'', and transposing it without changes to predict ''[[in vivo]]'' effects is not enough.<ref>{{cite journal
|vauthors=Louisse J, de Jong E, van de Sandt JJ, Blaauboer BJ, Woutersen RA, Piersma AH, Rietjens IM, Verwei M |title=The use of in vitro toxicity data and physiologically based kinetic modeling to predict dose–response curves for in vivo developmental toxicity of glycol ethers in rat and man
|journal=Toxicological Sciences
|date=2010
|volume=118
|issue=2
|pages=470–484
|doi=10.1093/toxsci/kfq270|pmid=20833708
|doi-access=free
}}</ref>