The dose is standardised in animals in mg/kg.
i just wanna extend the same treatment to cell lines and was trying to find a way to convert Drug dose from mg/kg to mg/ml ?
Dear Tushar,
The attached publication might be helpful in giving answer to some of the drugs.
Hoping this will be helpful,
Rafik
Dear Tushar,
The publication sent by Rafik is very useful.
Another simple way to obtain concentrations is to check if you have pharmacokinetic data from animals.
If you have in the same animal model the plasma concentrations obtained when giving the effective dose, you can use these concentrations for the cell lines. Generally you obtain a concentration range, corresponding to the maximal (peak) concentration and the minimal (trough) concentration (just before the next dose when doses are repeated). You can choose a concentration into this range, or the max and min, depending what you expect.
Moreover, if you have information about the % bound to plasma proteins, you can convert the plasma concentration, which is total concentration, to unbound concentration and then use this concentration in vitro (because the more often there are not plasma proteins in the culture medium).
Best regards,
Alain
Best regards,
Alain
Agree with both the suggestions above.
Additionally, you may be working on brain related cells. If so, it is quite difficult to correlate direct plasma conc (free or bound) as BBB limits the drug distribution to brain cells. So you need to understand there is no direct equation or correlation to convert the doses. As Alain clearly pointed out about another factor i.e. free and plasma protein bound drug conc. Free drug is actually responsible for the effect.
Also look for IC50 of the drug. You also need to check the cytotoxicity of the drug in the cell line at different conc (may be decided from PK data or previous literature or IC50) which will also help to decide the drug conc in other mechanistic studies. Also refer some literature on the drug you are evaluating.
Hope this will clear some doubt.
Regards
Sagar
Thanks Rafiq and Alain for the suggestions !
And Sagar, i second you on the point that there is no direct equation to convert the dose from animal models to cell lines.
And BBB indeed limits the entry of drugs to CSF.
Thank you Tushar for this discussion. Thanks to Rafik too for sharing valuable article. It is helpful for all. Thank you Alain and Sagar.
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