Yes you are right, you will have sum up of all the ingredients and convert it back to human dose (assuming that all the ingredients contains the active principles for the said indication)
Santosh,
These calculations are taken from the FDA guideline on the estimation of the safe starting dose in human. In the guideline, the values are given to calculate the animal dose to human dose and I have used the same values to back calculate the human dose to animal dose. You can also use Ghosh book on the Experimental Pharmacology, (I believe) to derive the interspecies dose calculation and both the method will give you the same results.
I wonder if anybody provide full reference? How do you calculate this dose? What is the scientific basis of multiplying human dose? I need clear explanation and calculation as well. Thanks in advance for raising this question. It is immensely helpful.
Kindly, is there an equation or formula to convert an oral dose from F344 rats to Wistar rats?, and if not, could i use the dose obtained from F344 rats to Wistar rats?
You have to use the conversion factor of 0.57 to convert G.Pig dose to rat dose based on the body surface area calculation. Here is the steps as mentioned in the Fundamentals of Experimental Pharmacology by M. N. Ghosh, 3rd Edition, Page No. 192.
Step 1: convert the mg/1000 g of G.Pig dose to mg/400 g b.wt.
Step 2: multiply the value with the correction factor 0.57 to convert the guinea pig dose at 400 g b.wt. to rat 200 g b.wt.
Step 3: Now you have dose for rat which is weighing 200g, now you multiply dose to 5 to get dose per 1000 g b.wt.
Hi Please correct me if I am wrong. I f I need to give meloxicam 7.5 mg tab per day dose (human dose) to a mouse. According to the conversion formulas mentioned above i should give 7.5 X 0.08= 0.6 mg . Is this right?
According to FDA guidelines for dose conversion, Human dose x Human km = Animal Dose x Animal Km. In these guidelines average human body weight is considered as 60kg so human dose will be 7.5/60 = 0.125 mg/kg. According to formula, 0.125 x 37 = mouse dose x 3. Mouse dose should be 1.54 mg/kg (37 is human km and 3 is mouse km). If the dose is calculated according to Freireich EJ, et al, 1966, the mouse dose will be same.
There are interspecies differences in CYP450 metabolism as well as absorption, other metabolic factors, distribution, excretion, etc., so the differences can be much larger than what is represented by a simple BSA calc. In order to use BSA, you really need to know these differences between human and the reference animal for that particular substance. If they are similar then BSA works, if not, it can be very different. I'm not aware of a good resource for this information unfortunately, I've had to research everything de novo on a per substance basis, which often takes a significant amount of time. If anyone else has a good resource for this it would be very helpful.
In your case, the HED is 96 mg (total dose for 60 kg b.wt). Dividing by 10 is the safety factor which you want to use if you think there are any adverse effects of the drugs in rats which are of concern in humans.
@ Yasameen Shaker
In your question, the human dose is 400 mg/day, correct? Assuming 60 Kg b.wt. of humans, hence the dose in mg/kg is 400/60 = 6.67 mg/kg.
To convert human dose to rat dose, multiply 6.67 by 6.2, which is 41.3 mg/kg rat dose or appox. 41 mg/kg. Does this answer your question?.
Through Allometric scaling method. Article A simple practice guide for dose conversion between animals and human
Point to be considered before converting a Traditional medicine:
Consider the literature for which is indicated for twice a day or thrice a day. If such mentioning is available, multiply the Human dose x 2 or 3 (depend on text) and convert it as per the scale.
Consider interval based dosing if it is metal based formulation (as per the text)
If any toxicity shown, don't moribund. Try traditional antidotes for easy recovery. (with prior approval from Ethics committee).
A webpage is created by CFTRI to convert doses from one species to another which includes human. Hence it is easy now that anyone can use this webpage for dose conversion across the laboratory animal species. the webpage
https://dosecal.cftri.res.in/index.php
DoseCal: a virtual calculator for dosage conversion between the animal species
Simple to try "Dose calculation conversion table" by Laurance & Bacharach, 1964
But, II suggested you to read this article (more detail with examples):
Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7(2):27-31. doi:10.4103/0976-0105.177703