Is there any formula or equation to predict the corellation between in vitro and in vivo studies.
How to calculate the dose in rats if IC50 value has been calculated for a compound in vitro?
Similarly, if the dose of any compound is know for rat/mice, then is it possible to calculate dose for cell culture?
I have seen this question asked several times on RG. The answer is no. There is no such simple relationship.
There is an entire branch of drug discovery science devoted to figuring out the effective in vivo dose of a drug: pharmacokinetics and pharmacodynamics (PK/PD). The dose cannot be determined by a formula based on an in vitro IC50 measurement, because there are factors involved in determining the exposure to the drug that can only be measured for a given compound in vivo: absorption, distribution, metabolism and excretion (ADME).
Fairly straightforward in vivo experiments can be used to measure the dose-exposure relationship (pharmacokinetics). Subsequently, in vitro techniques such as hollow fiber systems, or in vivo experiments, can be used perform the dose-fractionation experiments needed to measure the pharmacodynamic driver (exposure-effect relationship).
You also have to consider the tolerability of a compound to the test animals. For most compounds, the dose will be limited by toxicity.
Dear Andleeb!
You look at this guidanes , please:
3.3 Results Obtained with the Recommended Reference Chemicals in Two Standard Tests for Basal Cytotoxicity with Human and Rodent Cells
RC regression: log (LD50) = 0.435 x log (IC50x) + 0.625
New NHK NRU regression: log (LD50) = 0.498 x log (IC50) + 0.551 [R2 = 0.9356]
New 3T3 NRU regression: log (LD50) = 0.506 x log (IC50) + 0.475 [R2 = 0.9848
I have seen this question asked several times on RG. The answer is no. There is no such simple relationship.
There is an entire branch of drug discovery science devoted to figuring out the effective in vivo dose of a drug: pharmacokinetics and pharmacodynamics (PK/PD). The dose cannot be determined by a formula based on an in vitro IC50 measurement, because there are factors involved in determining the exposure to the drug that can only be measured for a given compound in vivo: absorption, distribution, metabolism and excretion (ADME).
Fairly straightforward in vivo experiments can be used to measure the dose-exposure relationship (pharmacokinetics). Subsequently, in vitro techniques such as hollow fiber systems, or in vivo experiments, can be used perform the dose-fractionation experiments needed to measure the pharmacodynamic driver (exposure-effect relationship).
You also have to consider the tolerability of a compound to the test animals. For most compounds, the dose will be limited by toxicity.
A point I should have made explicitly above is that the concentration of a drug administered to an animal is not constant over time (hence pharmacokinetics), whereas the concentration of a drug in an in vitro assay is constant over time. The response of the cells to the drug is likely to be affected by the concentration versus time relationship (pharmacodynamics). That is why it is necessary to investigate the PK and PD, in order to figure out the efficacious dose.
One more point: Most drugs bind to some extent to proteins that are abundant in the plasma, such as albumin, but it is usually only the unbound drug that has the desired effect. Therefore, it is also necessary to measure the plasma protein binding of the drug to predict the efficacious dose.
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