How do medical professionals figure out the lethal dose of drugs?

[Flatland]

How do medical professionals, scientists or whoever studies this stuff figure out the lethal dose of a particular drug? It's not like they can perform experiments on humans. Do they just test them on animals and then extrapolate that to humans? Do they find some kind of pattern from people overdosing? Or is it just an educated guess and a combination of the above?

 

[Simon Bridge]

How do medical professionals, scientists or whoever studies this stuff figure out the lethal dose of a particular drug? It's not like they can perform experiments on humans. Do they just test them on animals and then extrapolate that to humans? Do they find some kind of pattern from people overdosing? Or is it just an educated guess and a combination of the above?

... all of the above.

Researchers are not so concerned with the lethal dose as much as a reasonable safe dose. This properly starts with the stage 1 human trial thought they will likely be other information from animal tests and non-clinical use that will be taken into account. You don't go into a human trial without knowing that the initial dose is harmless. You can then step up doses and closely monitor the results.

Once a drug is on the market, the research does not stop - what may count as a lethal dose and in what circumstances is the sort of thing that can become clear after a few autopsies (and close rescues).

See: phases of clinical trials.
http://www.nlm.nih.gov/services/ctphases.html

 

[berkeman]

Please search LD50.

 

[cbrons]

In medical school pharmacology, the professor said that for a lot of drugs, there accumulates ample overdose data to sufficiently determine the number. Of course I'm not sure if this applies to all or even most drugs, so take it for what it is worth.
Source: Recent pharmacology lecture at an American M.D. school

It is interesting that if you search for "X drug overdose" on a program like Epocrates or LexiComp, if there is not an established LD50 there are usually links to individual case reports from toxicology centers about a patient who at one time took a whole bottle of something and then describes what went on to happen.
Source: personal experience using Epocrates