I do not think that you will obtain an "universal" response from the RG community according to my own 30-year experience in the in vivo domain (but only two months in the RG one).

There is neither “mathematical” nor “empirical” method(s) to determine the in vivo doses to be injected to rodents  from data obtained in vitro.

The only “mathematical” conversions that exist concern in vivo dose conversion between species (here attached).

You must first determine the maximal tolerated dose (MTD) in your rodent species (here mice). You can use “cheap” mice even if they are not of the same strain that the ones you will use for your in vivo activity experiments. There are indeed differences in “chemosensitivity” between various mouse strains, but this is definitively not a “killer issue”.

You should use 3 mice / group and 5 groups to determine the MTD for one given compound.

For curcumin, you have hundreds of articles published in this subject. The problems linked to curcumin is the way by which you will “solubilize” it for the in vivo experiments, and also the route of administration (per os versus i.p. versus i.v.).

So for curcumin, you have to take the “best protocol” published in the literature and administrate your “solubilized” curcumin at 5 doses to the groups of 3 mice each, i.e. “the Best Dose from the Literature on Mice” (I invent the BDLM dose for the purpose of my current message), the BDML/2, the BDML/4, the 2xBDML and the 4xBDML.

Then you “observe” during 28 days the behavior of the mice at least 3 times a day, you record the weight of the mice two times a week (usually on Monday and Thursday) and you record the deaths.

If everything is going “smoothly” your curcumin-related MTD should equal at least 2xBDML …

For your compound of interest, you should begin with a screening by 5 – 10 – 20 – 40 – 80 mg/kg as the doses to be administered  to the group of 3 mice each.

And same story as for curcumin.

Once you will have define the MTD for each compound (i.e. no severe adverse behavioral effects; no weight loss > 20% as compared to the first weighing procedure (to be performed the day before the administration); no death, and some other parameters), you will have to administrate your compound under MTD fractionated schemes, but the schemes will “heavily” depend on the model used.

I do not know what type of model you want to use, but if you “reveal” me this info, I can help you in defining the MTD fractionation scheme. Hoping that I understood well your message, I guess that you will use "cancer in vivo models".

Best regards

Robert

 Hi Dr. Robert,

Thank you so much for your immediate respond. Yes, you are correct that i will use cancer in vivo models. I'll be use a normal mice (strain later will be confirm). 

Let me simply.From my understanding, there are no others way to determine the doses except i need to optimize "maximal tolerated dose (MTD). In my cases, i need to define the MTD of curcumin and cisplatin(drug). Therefore, it means that before i started my in vivo study, i need to screening for the right doses by administered to the mice,right? Then , from here, how do i select the doses? (still unclear)

I just wondering, can't i just use the doses from previous jurnal who had try on curcumin and cisplatin? Will it makes any differences?

Dear Nazilah,

I think that it is better for you to perform the MTD determination by yourself for cisplatin and curcumin. I am sure that it will save you a lot of time and also of money because data are not so reproducible in the literature.

Once you have determined the MTD dose for each of your two compounds following an acute (single) administration, it is better to administrate the compounds chronically instead of acutely.

For very rapid growing tumors (killing the mice in about 3 weeks), in my research unit we administrate the compound of interest at MTD/4 five times a week (from Monday to Friday) during two consecutive weeks, with the first administration performed at the 3rd or 5th day post tumor grafting.

For "less" rapidly growing tumors (killing the mice in 3-8 weeks) we use MTD/4 (as we would do with cisplatin) or MTD/2 (as we would do for curcumin if a MTD is reached (depending on the route of administration), or "by default" 80 mg/kg if the MTD is not reached, administered 3 times a week (Monday - Wednesday - Friday) during 3 consecutive weeks, witht the first administration starting at the 5th or 7th day post-tumor graft depending on the model used.

These are all "empirical" rules issued from my own experience and these rules can certainly be optimized.

Here attached you have articles from our research unit illustrating you the type of in vivo experiments we performed.

Best regards

Robert

Dear Dr.Robert,

Thank you for the references. Let me go through of your paper. I need to understand the principal and i'll come back to you again. Thank you for your kindly help.

Dear Dr. Robert,

This is very comprehensive answer. Could you please clarify what will be the right dose if the mice model was same during both the MTD and the actual experiments?

Thanks in advance,

Wafa

Dear Nazilah,

Read this article it may be helpful

Hi all,

I have the same question about the in vivo dose for cancer mice.

Is the IC50 help to calculate the dose?

Thank you!

Tu

Calculating the appropriate dose for an in vivo study involves a series of considerations to ensure safety and efficacy:

By carefully planning and calculating the dose for your in vivo study, you can maximize the chances of obtaining meaningful and reliable results.

This list of protocols might help us better address the issue.