I have obtained result from in vitro which 10 ug/mL. How to predict what value of doses we need to use in the mouse (mg/kg). Is there any specific calculation to extrapolate the data to mg/kg? or we need to test the doses beforehand?
Your kind advice is greatly appreciated.
Hello there,
Its really very tricky as the translation may not necessarily augur well in vivo due to a lot of biological factors and interference. It will be easier to run a preliminary toxicity studies with a few mice to establish the LD50 intraperitoneally, from there you can deduce your ED50 and work with it.
Best of luck!
That depends on its route of administration. Generally for new drugs the blood volume of mouse (6-8% of the body weight) is used for calculation of dose administered. If the route of administration is oral, it will depend on the absorption process of new drug. If intravenously, you can calculate dose based in volume de mouse blood to achieve the effective concentration (10 ug/mL).
This is a first step . In case of the administered dose is not effective , you can go on increasing, as long as it is not toxic .
Yes, you can use the blood volume of the animal to calculate the dose. But I recommend that you make a pharmacokinetic study of the new drug to see if it is well absorbed by this route (calculate bioavailability). In the case of low absorption by this route, you have no way to know the real concentration of the new drug in the blood.
Ok...despite calculating and estimating the dose by pharmacokinetic study...if lets say based in in vitro,the result obtained 10ug/mL, and it has nearly similar result to commercial drug approximately 9.5ug/mL, can I initially refer the commercial drug i.p dose with the new drug? I mean, administered the same amount if it is not toxic of course.
Because I tried to find if there is a straight calculation from in vitro to in vivo.
Thanks again Marcelo Davanco.
Hello there,
Its really very tricky as the translation may not necessarily augur well in vivo due to a lot of biological factors and interference. It will be easier to run a preliminary toxicity studies with a few mice to establish the LD50 intraperitoneally, from there you can deduce your ED50 and work with it.
Best of luck!
hii
I have a similar situation wherein the effective conc in vitro was 0.04% v/v and 0.08%v/v. i want to try it in mice (weighing 30-35mg) thru oral feeding. what conc should i use. My LD50 studies using oral route is 10ml/kg ie greater than 9257.50 mg/kg.
It is imposible to extrapolate IC50 in vitro concentrations to in vivo MTD doses.
The active dose must be lower than the MTD dose, which must be first determined on healthy mice (without tumors).
Best regards
Robert
How can I convert in vitro enzyme inhibition into in vivo dose in mice or rat? Drug will be given orally.
As Robert mentioned, it is important to do acute oral toxicity study in healthy animals before your actual pharmacological studies. To my knowledge, there is no conversion formula from in vitro dose to in vivo dose. However, use of a standard drug in in vitro assay can help to find the approximate therapeutic dose of your unknown compound. If you compare IC50 of the standard drug and your compound, you will get a rough idea about the potency of your compound. Definitely, you can get the animal dose of standard drug. Based on your estimation of potency of your compound with respect to standard drug from in vitro study, you can roughly predict the animal dose of your compound.
For example, the IC50 of standard drug is 10 µM and effective animal dose is 20 mg/kg, p.o.
Suppose your compound shows IC50 of 100 µM, you can expect activity around 200 mg/kg, p.o.
However, the pharmacokinetic profile of your compound and the standard drug may vary and you might get different results.
If the oral toxicity of your compound is unknown, please follow OECD 423 guidelines to identify the MTD of your compound before proceed to actual pharmacological study.
All the best.
Dear,
There is no such formula to extrapolate an in vitro dose to in vivo studies. But you can opt to any of the following
1. If your molecule is completely new, then go for LD50 studies first to estimate the maximum dose which is safe to use. Then select any three doses below LD50 (I recommend you to go below LD25) and proceed for your pharmacological studies.
2. If you know the chemical class of the drug and its therapeutic area, then you can refer to any reported drug molecule in the same class for its dose and route of administration.
3. If you have synthesized new molecules by changing functional groups in any existing molecule (Refer point 2)
4. You can go for Pharmacokinetic and toxicity studies but it will consume lot of time. Again, if you know the chemical class of the molecule you can at least get an idea of the kinetics and toxicities of your molecule.
Hope this will be helpful. have a great day.
Hi There
we usually used the dose translation calculated by body surface area
HED(mg/kg)=animal dose (mg/kg)X(Animal km/Human km).
fully information you can find in this paper:
Article Dose translation from animal to human studies revisited
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