Why the differences in lethality of opioids between humans and animals ?

Qdar

Greenlighter
Joined
Dec 28, 2018
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10
No matter at how many sources you look: human lethal levels are low, animals levels are high. Of course getting the LD50 for humans isn't that practical but the differences are so huge.

An example for fentanyl: https://www.caymanchem.com/msdss/23580m.pdf oral TDLO woman 100 mcg/kg, oral LD50 rat 18 mg /kg, oral ld50 mouse 368 mg/kg.
The lowest lethal dose is not the same as the LD50, but estimated lethal doses for humans are much lower than for humans ? How come ? Is the information doctored ?
 

S.J.P.

Sr. Moderator: N&PD, DitM
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TDLO is not a lethal dose, it is a toxic dose. For obvious reasons there are no solid data on lethal doses of pharmaceuticals in humans.

Some compounds will be more toxic to various animals than they are to humans, and some will be the opposite. Although we are all mammals, metabolisms are different enough between a person, a pig, a mouse, a dog, and a monkey that you cannot take the toxicity of a compound in one of these animals and "translate" it to people... to the great chagrin of pharmaceutical companies.
 

novaveritas

Bluelighter
Joined
Jun 8, 2018
Messages
209
No matter at how many sources you look: human lethal levels are low, animals levels are high. Of course getting the LD50 for humans isn't that practical but the differences are so huge.

An example for fentanyl: https://www.caymanchem.com/msdss/23580m.pdf oral TDLO woman 100 mcg/kg, oral LD50 rat 18 mg /kg, oral ld50 mouse 368 mg/kg.
The lowest lethal dose is not the same as the LD50, but estimated lethal doses for humans are much lower than for humans ? How come ? Is the information doctored ?
correcting between species is an art. Humans are not big rats and vice versa however an human equivalent dose can be calculated from rat mouse or other animal data, this paper explains
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804402/

A genral rule is divide rat mg/kg by 5 or 6 or mouse by 12 and you are not going to be far out for human equivalent dose. The caveat is that some things are only toxic in animals or toxic in humans and not all animals because humans have different metabolic pathways. Pharma uses these human equivalint doses as a starting point in phase 1 trials.
 
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