From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.laboratory,sci.med
Subject: Re: Question: Dose Translation?
Date: 5 Jul 1999 10:13:44 GMT

In <377EBFEB.2FB6@netcom.ca> Tom Matthews <tmatth@netcom.ca> writes:
>
>Carey Gregory wrote:
>>
>> goober@nowhere.now (Goober) wrote:
>>
>> >In lab studies with mice that say the dose of drug
>> >x was 5 mg/kg, how exactly does this translate to
>> >humans? Does it mean for each kg of weight there was
>> >5 mg given, such that if the mouse is 2 kg it got
>> >(5 x 2) = 10 mg, and thus if a human weights
>> >500kg the comperable does is 2,500 mg? Or what?
>>
>> Yes, that's what it means mathematically, but dosages often don't
>> translate directly between species (or even apply at all -- what's
>> good for one species may be poison to another).
>>
>> By the way, if you've seen a 2 kg mouse running around, I suggest you
>> contact an exterminator immediately. ;-)
>
>And the same with a 500 kg human. :)
>
>One kg equals 2.2 pounds and a typical mouse mice weigh 50 grams ie.
>1/20 of a kg.
>
>For most vitamin/food nutrients, a direct weight conversion reduced by
>2-5 times because of the mouse's higher metabolic rate and daily food
>intake per kg, is not unreasonable.
>
>--Tom
>Tom Matthews



Comment:

   Mice need about the same RDA of most vitamins and minerals (save for
a few odd things like vitamin C, of course) as humans do, per
*calorie,* or Kg of *dry diet.*  Not per g of body weight, since (as
mentioned) the metabolism of an ad lib fed 25 g mouse (more common to
average, at least for young mice, than 50g--- which is a BIG mouse) is
maybe 15 kcals a day.  Or 1/2 kcal/gram/day for a mouse trying not to
be obese, like the average human American female.  That's 500 kcal/kg,
which is roughly 10 times the (specific) metabolic rate of an active
human adult.  Imagine weighing 70 kg and eating 35,000 kcal/day
(Cal/day).  That's 3 times the intake of even tour de France bike
riders, and to get that incredible sustained metabolic rate, those guys
have to put down nothing but fat fried noodles, vitamins, and sports
drinks, all day long.

   It's pretty close to the same thing for drug metabolism-- mice
generally are many times (5-10) better per gram than humans, due to the
fast metabolism. The only reason the LD50 lethal drug toxicity levels
are anything comparable between humans and mice is that is single dose
lethality, and is much more dependent on peak levels reached, in turn
due to volume of distribution size, which of course *does* scale
linearly with body weight, while metabolism does not.*  In trying to
chonically poison mice, the scientist finds it a much more difficult
job.

                                 Steve Harris, M.D.



* Total metabolic rate goes roughly as body size to the 3/4rds power
across mammalian species.  Specific metabolic rate (cal PER GRAM) goes
therefore as the -1/4 power of body weight.  A mouse weighs about
1/3,000th that of a human, and therefore is expected to have a specific
metabolic rate (and vitamin ratio per body weight, and heart rate, and
breathing rate) that is (1/3,000)^-1/4 =~ 7.4 times as large.  For
mice, it's actually a tad more than this general law predicts.  From
the square/cube of surface/volume ratio which is the essential problem
in heating mammals, whence all this metabolic stuff comes, you'd
predict exponents of 2/3 and -1/3.  But apparently mammals scale close
to 3/4 and -1/4, between species, while within species (dogs, say) it
is actually closer to the predicted 2/3rd power and -1/3 power.  Dogs
all have the same design, more or less (forget the Chihuahua, the
little monsters...)   But mammal species have more latitude.  So large
mammal species can apparently afford to run hot for better metabolic
reserve, and lose their hair (elephants, rhinos), while small ones have
problem getting calories enough to stay warm and have to eat several
times their body weight in insects evey day as is, compensate partly by
running metabolically a bit cool and growing very thick coats (shrews).