Dear Dr. Pramod

In continuation and supporting Dr. Jambou's comments, I would like to add my opinion too.

What I believe its never advisable to correlate a dose decided as the IC50 for any cancer cell line with any in vivo experimental dose in samples of murine origin.

First and foremost, both the experimental models are of entirely different origins unless we use carcinoma cell lines of mouse origins. So one dose defined in one system may exhibit little to a considerable extent of variation in the other.

Second, when doses are administered in vitro directly on cells growing as monolayers they happen to come in direct contact with the drugs which can lead to a sudden shock to a certain percentage of cells leading to senescence etc. At that very dose if administered in vivo, orally (ad libitum) the drug follows the alimentary route, where it is subjected to many digestive processes and other checkpoints. Finally if you see whats the effect at the level of xenografts or bone marrow cells the effect will definitely be slightly to considerably different.

There are even different IC50 values for the same drug in two different cell lines like on drug may show a IC50 drug 55 microgram in MCF-7 and the same drug will click at 170 microgram in HeLa!

In addition to that in vivo there can be three routes of administration, orally intraperitoneally or intravenous. The effects among them only show different results graphically.

My suggestion will be to determine the IC50 value for cell lines (different for each cell line) and the LD50 for mouse and rats in different experiments; and like this continue with the later experiments.

I guess this approach will be tedious but more accurate :)

This is a good and interesting topic.

in vivo, the cells see the blood or plasma concentration of the drug, unless it is lower because they are some distance from the capillaries and the drug is metabolized by the intervening cells. thus, one should use the plasma concentration for in vitro experiments.

As Christopher siad, in this way (in vivo > in vitro) we can use plasma concentration for in vitro experimentation.

In the way in vitai>in vivo, it's classic to use the in vitro media concentration as first in vivo doses. And you have to can mesure plasma concentration in animals to ensure you'll obtain the same plasma concentration levels than in culture media. If not, increase injected dose, but insure at the same time there is not toxic effects (the second step in experiments).

Best regards

Didier

thank you all for sharing your valuable information regarding this.

from the above comments, what i understood is, one have to focus on plasma concentration of the drug in invivo analysis, rather than the administering concentration and dosage.

and most probably there would be changes in the concentrations of drugs that might have used for the in vitro analysis.

So my next querry is, is it necessory to find out LC50 or LD50 dosage in invivo analysis as we perform that in invitro?

or can we start the invivo analysis from the concentration we optimized in invitro?

Dear Promod Darvin,

Unfortunatly, and at present, in vitro data are not direcly correlated with in vivo data (one reason being in vivo drug metabolism of drugs that are not the same than the one of cells in vitro).

And especially LD50 reffering to organsim toxicity; even if in vitro lethality on cells could be well correlated with general toxicity in animals. It's not yet recognized that we can substitute in vitro experiments with in vivo ones on animals, at least for official draft asked for drug commercialisation.

Best regards

Didier J

Dear Dr. Pramod

In continuation and supporting Dr. Jambou's comments, I would like to add my opinion too.

What I believe its never advisable to correlate a dose decided as the IC50 for any cancer cell line with any in vivo experimental dose in samples of murine origin.

First and foremost, both the experimental models are of entirely different origins unless we use carcinoma cell lines of mouse origins. So one dose defined in one system may exhibit little to a considerable extent of variation in the other.

Second, when doses are administered in vitro directly on cells growing as monolayers they happen to come in direct contact with the drugs which can lead to a sudden shock to a certain percentage of cells leading to senescence etc. At that very dose if administered in vivo, orally (ad libitum) the drug follows the alimentary route, where it is subjected to many digestive processes and other checkpoints. Finally if you see whats the effect at the level of xenografts or bone marrow cells the effect will definitely be slightly to considerably different.

There are even different IC50 values for the same drug in two different cell lines like on drug may show a IC50 drug 55 microgram in MCF-7 and the same drug will click at 170 microgram in HeLa!

In addition to that in vivo there can be three routes of administration, orally intraperitoneally or intravenous. The effects among them only show different results graphically.

My suggestion will be to determine the IC50 value for cell lines (different for each cell line) and the LD50 for mouse and rats in different experiments; and like this continue with the later experiments.

I guess this approach will be tedious but more accurate :)

Dear Darvin

I think it may be better to determine your drug dosage in vivo experiment based on the data of pharmacokinetic analysis. You know, oral administration means your drug have to be metabolized before its functioning, possibly degraded into several matoblites in stomac and intesistin, then these matoblites enter into plasma, which matoblite is the effective gredient? Then try to find the quantity relation between your drug and its effective gredient. As such, you can determine your drug dosage for in vivo experiments easily. just for reference.

Can anyone help with a review article, research article, website etc.. on the topic above?