How to translate LD50 from rats/mice to humans?

[Snafu in the Void]

I just happened to be looking at the LD50 of morphine sulfate, which is stated to be 600mg/kg in mice (oral dosing). Unless I am grossly mistaken, this means 600mg of morphine would kill a mouse that weighed 1kg 50% of the time (?).

I was curious how to go about translating this data into what the human LD50 of morphine would be? Is there any real way to do this with a reasonably low margin of error? Clearly humans are different than mice, so we likely cannot simply scale up from bodyweight alone even after adjusting for tolerance.

Anyone knowledgeable here?

I'm simply curious on the matter. I don't plan on telling anyone the exact amount of drugs they can take before dying, as that would be foolish.

 

[paracelsius]

Multiply mice LD50 (mg/Kg) by 0.081 to get humans values: 600mg/kg x 0.081 = 48.6mg/kg. That would translate to about 3.4g for a average 70kg human. But be very very careful extrapolating mice or rats LD50 data to humans!!! especially with opioids! example: rats have a pretty high tolerance to fentanyl compared to humans!!! too bad LD50 cannot be measured in humans.... obviously!!!! tho I ethically abhor killing any animal to get a lethal dose so humans can use the drug safely!? not for the benefit of the animals! anyway.....

for rats multiply by 0.162. google allometric conversion to get calculation table for most animals to humans data conversion factor. iirc there is a site where you just plug in the LD50, IC50, ED50 ..etc it will give you the values in different animals humans..etc
Lethal dose LD50 is the dose in mg/kg that kills 50% of the test subjects.

 

[Snafu in the Void]

@paracelsius thank you

 

[Skorpio]

I'd be really careful to only use these values as a reference. There are a lot of physiological differences between rodents and humans (and other animals and humans), so some toxicities that are unique to humans will not be generalized.

This can especially be the case with metabolic enzymes where variation by species makes mouse models fairly inaccurate at times. Medicinal chemists will usually look at drug metabolism using human hepatocytes which express the right forms of enzymes, but lack the interactions that occur in multiple organ systems, and then multiple animal models, especially when individual enzymes occur.

For example these are clinical trials that ended in death due to toxicities unique to humans that were not predicted.

BIA 10-2474 - Wikipedia

en.wikipedia.org

Theralizumab - Wikipedia

en.m.wikipedia.org

 

[fastandbulbous]

You can't really, due to different metabolic pathways. On a mg/kg basis, dogs are way more tolerant of opioids. With cats, paracetamol is horribly toxic, as they lack certain enzymes to detoxify and eliminate it (NEVER give a drug safe for humans to other species. That's why vets have an incredibly long degree). I mean, mammalian biochemistry can differ vastly from one species, to another (only two species need ascorbic acid in their diet; all other species can synthesise it. The two species: humans and guinea pigs - like I said, no rhyme or reason

 

[RoBoInSlowMo]

Many years ago, I gathered all the information regarding potency to common opioids, and compiled a conversion list. I did this by looking at LD/50 as mentioned in this post, information regarding potency, smallest and largest available pharmaceutical dosages and more. For example, it is widely accepted it only takes two milligrams of Fentanyl to kill the average intolerant person. You can take this information and compare the potency of two different opioids and get a fairly accurate conversion, and from there further fact check it. This took me around three days to complete, and was posted nearly three years ago, so do keep in mind it is dated. (Not to write, most of the time was spent compiling information and resources, I wish I wouldve saved that somewhere as well)

Opioid potency conversion chart:

 

[RoBoInSlowMo]

(Mind you some opioids have a greater effect on the raspatory system, kind of like how certain stimulants are more cardiotoxic than others - this means it may require less to overdose at comparable dosages essentially)

(Fentanyl is a great example of this)