17 replies to this topic

[ScienceGuy]

Hi everyone,

I have noticed that fairly often the matter arises regarding what dosage is applicable to HUMANS when referencing the dosage(s) in a study conducted on ANIMALS.

The most common instance is RODENT STUDIES wherein the dosages mentioned are applicable to either RATS or MICE; and wherein there exists the need to calculate what is the HUMAN EQUIVALENT DOSAGE (HED).

Therefore, I thought I'd post here the details regarding precisely how the HED can be calculated.

In short, the relevant formula is as follows:

HED (mg/kg) = Animal Dose (mg/kg) x [Animal K_m / Human K_m]

Human K_m = 37

Mouse K_m = 3

Rat K_m = 6

EXAMPLE:

Say a STUDY conducted on MICE reports that a dosage of 5mg/kg was used; what is the HED?

By calculation, the HUMAN EQUIVALENT DOSE (HED) = 5 x [3 / 37] = 0.405 mg/kg

For further details see attached file "Dose translation from animal to human studies"

Attached Files

•  Dose translation from animal to human studies.pdf   86.05KB   104 downloads

[Nattzor]

Isn't the Km based on a person with the weight of 60 kg? So you (should) change it in the formula so it "fits" your weight?

[ScienceGuy]

Isn't the Km based on a person with the weight of 60 kg? So you (should) change it in the formula so it "fits" your weight?

Actually, no

Please kindly note that the scaling purely according to body weight is precisely what is the common mistake that needs to be avoided.

K_m = Body weight (kg) / Body Surface Area (BSA) (m²)

Hence, if you wanted to be absolutely accurate and adjust for weight differential then you would also need to factor in Body Surface Area (BSA) differential too.

As such, to avoid matters being overcomplicated, since the K_m for adult human won't in fact vary massively I would simply use the 37 figure, unless you wish to complete the more complex calculation incorporating both Body Weight and Body Surface Area (BSA) differentials

Edited by ScienceGuy, 14 August 2012 - 05:01 PM.

[Cerebro]

Thank you.

+
http://www.longecity...animal-studies/

[polymathic]

Very very very very useful Scienceguy.

[ScienceGuy]

Very very very very useful Scienceguy.

Thank you kindly for the positive comment. I am very glad to hear you find it useful

[nightlight]

For further details see attached file "Dose translation from animal to human studies"

I get error message (no permission) when trying to download that file. Is there a fix?

[ScienceGuy]

I get error message (no permission) when trying to download that file. Is there a fix?

Here's the document for you:
(N.B. Click on each page to have it open enlarged in a new window)

Edited by ScienceGuy, 29 August 2012 - 07:20 PM.

[nightlight]

Here's the document for you:

Thanks, it's a useful little paper.

[stolpioni]

What if the dosages are listed as "per mouse", lets say "20ug per mouse". How much would you give a human?

[kurdishfella]

can anyone explain to me how much https://www.ncbi.nlm.../pubmed/9651122 this would be?

 

100 x (6/37) = ??

(didn't go to school)

[kurdishfella]

is it 16mg? So I weight 80kg I would need 80x16mg = 1280mg?

 

Edited by farshad, 26 June 2018 - 04:41 AM.

[OP2040]

Does anyone know how HED applies to solutions.  I'm trying to translate for eye drops.  The drug is a 10% solution, and the dose is just 3ul.  My understanding is that the solution can be made in any amount as long as it's 10%.  So the HED would just be on the 3ul.  Any ideas?

[ScienceGuy]

Does anyone know how HED applies to solutions.  I'm trying to translate for eye drops.  The drug is a 10% solution, and the dose is just 3ul.  My understanding is that the solution can be made in any amount as long as it's 10%.  So the HED would just be on the 3ul.  Any ideas?

It does not matter whether the form is solid or solution, HED applies in precisely the same way. Whatever the dose is you calculate the HED using the aforementioned formula. So yes in this particular instance if the dose is 3ul then you would use that to calculate the HED

 

[OP2040]

Using just x12.3 for mouse to human, would be ~37ul.  A standard eye dropper drop is supposedly can range anywhere from 30-60ul depending on where you are and manufacturer.  I suppose that works as a guesstimate.  Obviously given that this is an eye solution, I want to do a dose escalation and start very low, even though the compound has been studied extensively, even in eyes, albeit not as much in human eyes.

 

Does that sound right?  I'm handicapped with the metric system as an American, but it seems fairly straightforward.  I'm just not sure if a straight conversion is the rigt way to go for a liquid solution.

[OP2040]

Thanks for the quick reply science guy.  The part about the formula that's throwing me is the mg/kg.  If I just plug the 3ul in, I get .24ul which doesn't make any sense, unless maybe it needs to be multiplied by 100 at the end.

[ScienceGuy]

Thanks for the quick reply science guy.  The part about the formula that's throwing me is the mg/kg.  If I just plug the 3ul in, I get .24ul which doesn't make any sense, unless maybe it needs to be multiplied by 100 at the end.

 

Well firstly, obviously you need to ensure that whatever this substance is it is safe for application with respect to human eyes. You don't want to be taking risks.

 

Furthermore, please note that the HED calculation relates to systemic application. Something which is applied topically or to the eyes, wherein the mechanism of action is not systemic will not necessarily apply.

 

What is the substance and what are you wishing to use it for exactly?
 

Edited by ScienceGuy, 16 November 2019 - 05:19 PM.

[OP2040]

Anyone that does any intervention without supervision is taking a risk, and most people on this board do so.  The question is more whether the risk is low, and mitigated further by proper protocols and caution.  I am fairly risk averse, so no worries there.  I don't want to get into a discussion about the experiment itself, though I may change my mind afterwards.

 

I see your point about systemic vs specific conversions.  While I do believe that topical eye applications can reach the retina, and even the brain, it's common knowledge that they are far from systemic.  So I am flying blind a bit, though I'd be shocked if there was never an attempt to translate a topical ocular treatment from mouse to human. The only difference I've read about is that the mouse (and most non-human mammals) lacks a macula.  Aside from that it should be quite similar.  I'll just be conservative and use dose escalation.