I am working on a new developed drug for its anti-tumor effect. Currently I am finishing the in vitro part with tumor cell line experiment. I have tested the IC50 in vitro. Now I want to inject my drug to nude mice by i.p. So my question is how can I get to know which drug concentration should I use. eg. my in vitro concentration for cell culture is 10uM. Which concentration should I use for nude mice?
And I checked some information, most people were saying you need to do a LD50 test, or do the pharmacokinetic (PK) and pharmacodynamic (PD) study first. Then my question is can somebody tell me more in details how should I do it? And is there an rough and easy way instead of the complicated pharmacokinetic (PK) and pharmacodynamic (PD) study?
Thank you all in advance!
This is actually a difficult question. Are you attempting to find a dose in vivo that will result in killing half the cells in a tumor? You would need information on the pharmocokinetics of your compound in vivo -- in particular, you would need to have information about the concentrations achieved in the tumor (and other tissues) at various times and doses of your compound.
Dear Richardson,
Thank you very much for your answer. Actually for my experiment the situation is I will build mice bearing tumors on nude mice first then I will treat the mice using my drug by i.p.(Intraperitoneal injection). So currently I want to find the suitable concentration to be administered for "therapeutic" purposes. Because the drug is effective in vitro so I hope the in vivo experiment will also demenstrate the therapeutic effect and of course without serious toxicity.
Best Regards,
Jun
Not an easy question without pharmacokinetic information in the same specie.
Using a general thumb rule you might use the following information.
You need to know the molecular weight of your compound. Let's assume is 300 D
This mean 300 g/mol = 300 ug/uMol
Then, as you mention for example, you have IC50=10uM
this means 10uMol/L /1000 mL = 0.010 uMol/mL
To get the concentration: 0.010 uMol/mL * 300 uMol/mL = 3ug/mL
This is the concentration corresponding to your IC50 in vitro. If you don't have any pharmacokinetics in vivo you may consider, that in general, following i.p. administration you may reach this concentration in vivo with a dose approximately between 3 and 10 mg/Kg.
Of course you need to use the actual vaues to get the real equivalent concentration.
However it would be advisable to have preliminary PK and toxicity evaluation before starting efficacy models.
I hope this can be of help.
Before greeting you, like Miss Jun, i also have the same problem. I have done research using the dose of extract into in vitro then the dose i want to do to mice (in vivo). My question is how to change the concentration in vitro to in vivo if i don't have an LD50.
Thank you
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