how to calculate a dosis for mice - (Nov/02/2007 )

hi guys,

I have to calculate the dosis for my mice experiment and do not know exactly how?! I want a concentration of 5umol/per dosis and I want to give it i.p. and p.o.! Now the question is, how much g/kg I need?

Can someone give me the answer, please?!

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I am not sure I understand your query.
your want 5 umol/per dosis.
It means you want to give to each mouse 5 umol ?!
The only thing you need to know now is the molecular weight of your compound.

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a more exact information would be molality f.i. µmol/g instead of µmol/dosis

in your case "per dosis" may refer to an average sized/weighing mouse;

simply calculate your g from µmol by utilizing Mw of your substance;

then estimate what an average mouse weights, considering line, gender and age

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Hi you both!
thanx a lot for your answers

Here are more informations: we tried our inhibitor in vitro first and there the best concentration worked was 5 umol. therefore we want to test this concentration in mice. so, now I have to calculate which dosis in mg/kg I have to give one mouse that I have a concentration of 5umol and then calculate how much I have to give a mouse of 20gramms. but I really don't know how to calculate this because chemistry in school is long long away and I really can't remember it. and in my study I didn't learn such topics. so I really need some mathematical advice, please!

the molecular weight is 451.592! can you explain me how to calculate it?

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you need to know the volume of blood in a mouse.
I don't remember. try to find.
You need also to know the biodisponibility of your compound, depending on the way of administration (per os, intraveinous, ...)

5 umol is not a concentration, it's an amount. I guess you meant 5 uM which is 5 umol/L.

the molecular weight is 451.592
you have have 451.592 ug per umol
451.592*5 ug in 5 umol
and 5 umol in 1 liter
so you have 451.592*5 ug/L = 2.258 mg/L = 2.258 ug/mL

2.258 ug/mL (let's say 2 ug/mL) is the concentration you would like in the blood of the mice. (you should try several concentrations around 2 ug/mL)
Once you know the volume of blood and the biodisponibilty, you should be able to calculate the amount (ug) of your compound to administrate.

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hi missile,

thank you so much for your help!
and yes, you are totally right, that I meant 5uM

I'm going to look up the rest (blood volume etc.). think, I will be able to get this by my own... Do you know, how much liquid I can give per os for one dosis (I think the maw can content maximum 1,5ml). And how much is best for i.p.? what can you suggest me and do you have some other advice in this topic?

It's really good that one can talk to some people with more experience!

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Sorry, not so much experience with mice.
If you a create a new topic asking theses questions, I'm sure you will have plenty of answers.

To overcome the problem of biodisponibility, I would use i.v. or i.p.

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ok, thanks anyway!!! (and sure, I will start a new topic )

greetings

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First, I assume your “5 µmol/dosis” means you want to give 5 µmol per mouse. You need to know the volume of distribution; for most mammals a good general rule of thumb is 6% of body weight. Therefore, for a 20 gm mouse, the volume of distribution would be 20 x 0.06 = 1.2 ml. So, 5 µmol per 1.2 ml = 5 µmol x mw of drug, i.e.µg/µmol = # of µg to inject. For a mouse that size, I would not inject more than about 150 µl total, so you then just prepare a stock solution such that you will deliver that number of mg in 150 µl. I assume you want to give it ip. Ok, that’s all fine, but as usual, things are NOT THAT SIMPLE.

Direct translation of an in vitro dose to in vivo is not always possible. The reason is, you do not know the pharmacokinetics of your compound. For example, if in plasma, 90% of your drug is bound up by plasma proteins, and you’re giving 5 µmol in 150 µl, as described above, the animal’s receptors for that drug are only going to see 10% free compound, i.e. 0.5 µmol. Therefore, the dose you need to use in animal studies may greatly exceed what works in vitro. Similarly, you also do not know how this drug is metabolized—maybe the liver snatches most of it up, converts it to some metabolite which then gets excreted by the kidneys. So, because of these unknown variables, you will need to perform careful dose-response studies in mice using a range of doses bracketing your 5 µmol/mouse dose—e.g., 0, 0.5, 5, 50, 500 µmol/mouse (maybe higher), using about 6 mice per dose. Here’s what I would do: Start with several mice and give them a large dose, say, 500µmol. If you get a response, great. If not increase it to say, 1 mM or something. As long as it isn’t toxic, you’re ok. Once you find a high dose that works, just back off the dose in subsequent studies until you see where the threshold is. Then for future studies use the lowest dose that gives you a statistically significant effect. Dose-response studies are tedious, but they are ESSENTIAL.

Good luck.

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