biology

In vitro to in vivo extrapolation

In vitro to in vivo extrapolation is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand In vitro to in vivo extrapolation rather than just read about it. In short: In vitro to in vivo extrapolation (IVIVE) refers to the qualitative or quantitative transposition of experimental results or observations made in vitro to predict phenomena in vivo, biological organisms. The problem of transposing in vitro results is particularly acute in areas such as toxicology where animal experiments are being phased out and are increasingly being replaced by alternative tests.

Key takeaways

In vitro to in vivo extrapolation belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect In vitro to in vivo extrapolation to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of In vitro to in vivo extrapolation from memory before moving on to harder problems.

Reference excerpt

In vitro to in vivo extrapolation (IVIVE) refers to the qualitative or quantitative transposition of experimental results or observations made in vitro to predict phenomena in vivo, biological organisms. The problem of transposing in vitro results is particularly acute in areas such as toxicology where animal experiments are being phased out and are increasingly being replaced by alternative tests. Results obtained from in vitro experiments cannot often be directly applied to predict biological responses of organisms to chemical exposure in vivo. Therefore, it is extremely important to build a consistent and reliable in vitro to in vivo extrapolation method. Two solutions are now commonly accepted:

(1) Increasing the complexity of in vitro systems where multiple cells can interact with each other in order recapitulate cell-cell interactions present in tissues (as in "human on chip" systems). (2) Using mathematical modeling to numerically simulate the behavior of a complex system, whereby in vitro data provides the parameter values for developing a model. The two approaches can be applied simultaneously allowing in vitro systems to provide adequate data for the development of mathematical models. To comply with push for the development of alternative testing methods, increasingly sophisticated in vitro experiments are now collecting numerous, complex, and challenging data that can be integrated into mathematical models.

Pharmacology IVIVE in pharmacology can be used to assess pharmacokinetics (PK) or pharmacodynamics (PD).. Since biological perturbation depends on concentration of the toxicant as well as exposure duration of a candidate drug (parent molecule or metabolites) at that target site, in vivo tissue and organ effects can either be completely different or similar to those observed in vitro. Therefore, extrapolating adverse effects observed in vitro is incorporated into a quantitative model of in vivo PK model. It is generally accepted that physiologically based PK (PBPK) models, including absorption, distribution, metabolism, and excretion of any given chemical are central to in vitro - in vivo extrapolations. In the case of early effects or those without inter-cellular communications, it is assumed that the same cellular exposure concentration cause the same effects, both experimentally and quantitatively, in vitro and in vivo. In these conditions, it is enough to (1) develop a simple pharmacodynamics model of the dose–response relationship observed in vitro and (2) transpose it without changes to predict in vivo effects. However, cells in cultures do not mimic perfectly cells in a complete organism. To solve that extrapolation problem, more statistical models with mechanistic information are needed, or we can rely on mechanistic systems of biology models of the cell response. Those models are characterized by a hierarchical structure, such as molecular pathways, organ function, whole-cell response, cell-to- cell communications, tissue response and inter-tissue communications.

References

Blaauboer, BJ (2010). "Biokinetic modeling and in vitro - in vivo extrapolations". Journal of Toxicology and Environmental Health, Part B. 13 (2–4): 242–252. doi:10.1080/10937404.2010.483940. PMID 20574900. S2CID 36228477. Quignot N., Hamon J., Bois F., 2014, Extrapolating in vitro results to predict human toxicity, in In Vitro Toxicology Systems, Bal-Price A., Jennings P., Eds, Methods in Pharmacology and Toxicology series, Springer Science, New York, USA, p. 531-550

Worked examples

Example 1 — a first encounter with In vitro to in vivo extrapolation

Start with the simplest possible case. Write down what In vitro to in vivo extrapolation claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to In vitro to in vivo extrapolation before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about In vitro to in vivo extrapolation ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of In vitro to in vivo extrapolation

In research: In vitro to in vivo extrapolation appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses In vitro to in vivo extrapolation in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: In vitro to in vivo extrapolation is common in secondary-school and first-year university syllabi. It links to neighbouring topics Alternatives to animal testing, Latin biological phrases, so understanding it makes those chapters shorter.
In everyday life: Look for In vitro to in vivo extrapolation outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

Ask Teacher Smith questions about this articleOpens your AI tutor with a question about “In vitro to in vivo extrapolation” →

Affiliate

Preply — study more efficiently by working with a personal tutor. 50% off.

How to study In vitro to in vivo extrapolation in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what In vitro to in vivo extrapolation means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain In vitro to in vivo extrapolation out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is In vitro to in vivo extrapolation in simple terms?

Why does In vitro to in vivo extrapolation matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study In vitro to in vivo extrapolation?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on In vitro to in vivo extrapolation.