I am working on animals with a new compound. Already I have worked on cell lines with the same compound. How can I fix my doses for animal study using my cell lines data.
Hi, It is totaly impossible to make any equivalence between a pharmacological action in vitro on cells in culture and in vivo effect even to help you bay a range of possible ratio . First the effect depends of the cells used and is specific from the cells and may be species if you celle line or primary culture is comming from another species ; second, because of isolated cells you eliminate all the regulation steps due to extracellular matrix (including other tissues interactions). The pharmacokinetic also differs and drugs could be absorbed, and relaesed in the different compartiments of the multi cells tissues of body that culd modulate the effect (and you can also add the chronobiology of a full organism not found at the cell level). Third, one drug could be toxic at the drect cell level and not when injected in animals because of metabolism and process of détoxification by lungs and liver for example. At the opossite, an efect can be seen at the cell level and not at all at the in vivo full organism level because, the drug will be eliminated, metabolisate/inactivate totally of for a part. Please in physuiology and pin vivo pharamcological experiment DO NOT TRY to relate local invitro effect and In viivo effects. It is a general problem in publications and it is in fact very scarce effect comparable at the two levels: the big majority of paper published in cell models never found any application at the in vivo level!! This methods are complementary, could help to understand possible local effect but do not be used to imagine a possible in vivo action. Some new and sophisticated model of co-culture of cells mimiking some tissus complexity and intercation try to be closer to the real in vivo situation but that remains far from the reality.
I totally agree with Dr. Marnet. You should try titration of compound in vivo study.
Good suggestion Dr. Marnet, I think in the development of new active compound you can start with standard preclinical test, like general toxicological test (acute, chronic etc) and its efficacy using diseases animal model.
As already said, it is impossible to translate in vitro results into animal doses. Furthermore it is impossible to predict toxic side effects.
You can however do a very important thing: you can determine in vitro the intracellular concentration of your drug required to obtain the desired effect: when doing your phase-1 study in animals you can measure if you can obtain such a concentration in plasma, or in circulating mononuclear cells or (the optimum!) in tumour cells with an acceptable toxicity. This is an excellent way to integrate in vivo and in vitro research.
Thank you all for your valuable inputs. Now i got idea to work on it.
you can also go for toxicity test on mice to get dose dependent toxicity. If your compound is not reported anywhere I don't think so. Compound of similar structure must be in literature, use chem web like data base to explore the particular compound.
- Badges
- Science topic
- Similar topics
- Chemistry
- Pharmacology
- Pharmaceuticals
- Drugs