Hi

The dose mentioned 20 ml/Kg is not actually a dose, it is a volume of fluids containing certain weight of a certain substance (drug). So, if it is just about dividing this volume; its easy to divide the volume required for each rat according to its weight into 2. For example, if a rat is weighing 200 g, this means it has to be injected with 4 ml, so you can divide into 2 x 2 ml. But for the time difference to be kept between each of them, it is according to the nature of the drug given, its kinetics and action. I advice to refer to a previous research having the same drug or substance used and take it as reference.

Hi

The dose mentioned 20 ml/Kg is not actually a dose, it is a volume of fluids containing certain weight of a certain substance (drug). So, if it is just about dividing this volume; its easy to divide the volume required for each rat according to its weight into 2. For example, if a rat is weighing 200 g, this means it has to be injected with 4 ml, so you can divide into 2 x 2 ml. But for the time difference to be kept between each of them, it is according to the nature of the drug given, its kinetics and action. I advice to refer to a previous research having the same drug or substance used and take it as reference.

Hii Laxit Bhatt

you should know original conc of material, appropriate amount that will dose for experimental animals (mice 1ml = 100 gm) and weight of animal (based on each animal weight different from other ) .

HI, Amina and Eslam.

Thank you for your answers.

I would like to know if  there is a guideline or a reference material that says it is okay to divide dose volume of 20 ml/kg into 2 doses. Also, if it is, does the guideline mention about the time difference between two such doses, like, 6-8 hours between each of the dose. Like you said, it is generally dependent on the concentration and the nature of the drug to be administered, but is there a general consideration of time difference between two doses? We also need to put animals on overnight (rats) and 3-4 hours fasting (mice) before we can administer the dose. So, if we are to divide the dose volumes into 2, do we need to put the animals for fasting before the second dose?

Hi Laxit

Still the issue is depending on the drug nature and kinetics. Any way, try to keep 8 hours of fasting for rats for example (overnight), inject at 8:00 am once, let them eat and drink once, then put them on fasting once again and give them the second dose by 5:00 pm. This can be applied if the dose must necessarily be divided into two. Ensure first that your substance duration of action is short and that it must be given on divided doses and go to a reference which did the same. I think you can find in the reference many useful details.

Regards

Hello Anne,

I want to conduct an acute toxicity study in wistar rats and ICR mice. Now, the problem I face is the viscosity of the formulation. And hence I was wondering, if I could administer the compound in more than one dose, so as to relive the animal of extra stress caused due to such a viscous formulation. And, in order to do that, I need to put the animals on fasting before I dose them. So, the question was if its possible to divide the dose (which the OECD TG 420, 423 or 425 do not clearly mention about) and how long should the fasting time period be for both the species?

(It is important to note that, I will need to continue fasting of animals if I am administering a second divided dose)

I think OECD 420 gives you the answer, although what might be considered an "unusual circumstance" requiring multiple fractions might need clarification.

PROCEDURE

Administration of doses

14. The test substance is administered in a single dose by gavage using a stomach tube or a suitable intubation canula. In the unusual circumstance that a single dose is not possible, the dose may be given in smaller fractions over a period not exceeding 24 hours. 

15. Animals should be fasted prior to dosing (e.g. with the rat, food but not water should be withheld over-night; with the mouse, food but not water should be withheld for 3-4 hours). Following the period of fasting, the animals should be weighed and the test substance administered. After the substance has been administered, food may be withheld for a further 3-4 hours in rats or 1-2 hours in mice. Where a dose is administered in fractions over a period of time, it may be necessary to provide the animals with food and water depending on the length of the period.