How valid of an assumption is using mg/kg for drug dosage?

[Simfish]

Okay, basically, the more mass you have, the more drug that's needed to exert the same effect on you.

But is it really linearly proportional like that?

I mean, if you increase your body mass, you're not going to increase the amount of blood in your major arteries and veins. The amount of blood in them is fairly fixed (or is it?)

Rather, you'll increase the amount of blood in more peripheral blood vessels. How much does this amount of blood scale with increased mass? Is fat tissue more vascularized (on average) than other types of tissue? Or not? Furthermore, is it a valid assumption that a drug will diffuse "equally" throughout the body, including all of the body's capillaries?

 

[JaredJames]

I mean, if you increase your body mass, you're not going to increase the amount of blood in your major arteries and veins. The amount of blood in them is fairly fixed (or is it?)

Well, let's start simple, does a baby have the same size heart as a full grown adult? Does a baby have the same size arteries as an adult? and so on.

Can you see my point here?

 

[Simfish]

Well, let's start simple, does a baby have the same size heart as a full grown adult? Does a baby have the same size arteries as an adult? and so on.

Can you see my point here?

Yes, I definitely see your point there, although it wasn't the picture I was looking at.

What I was thinking about is more like this: Would a fully grown 150kg human adult have 3 times the blood volume of a fully grown human adult weighing 50kg?

 

[JaredJames]

Well all of the living cells in your body require a blood supply. If you have a larger amount of said cells, would you need more or less in the way of blood transportation and blood volume?

 

[Simfish]

That's true. But you could divide blood volume by body mass for a set of humans. The real question is - is it a linear function? Or could it be more nonlinear than we realize? (if so, that could make the mg/kg metric less reliable than we think).

 

[JaredJames]

Well if you know the average blood supply to 1kg of body mass, then it is a pretty linear function.

You could take many samples of body mass at 1kg and check to ensure they all have roughly the same value.

 

[Simfish]

Well if you know the average blood supply to 1kg of body mass, then it is a pretty linear function.

You could take many samples of body mass at 1kg and check to ensure they all have roughly the same value.

That is the intuitive way to generate the hypothesis. But we would also need to compare this value between different people - because thin people owe a greater proportion of their blood volume to their major blood vessels - whose volume cannot increase with body mass. It's entirely possible that it's a nonlinear function of body weight among adult individuals of a given height. (it's also entirely possible that the function could be non-linear for increases in height too, although I think this is less likely).

 

[bobze]

Okay, basically, the more mass you have, the more drug that's needed to exert the same effect on you.

But is it really linearly proportional like that?

I mean, if you increase your body mass, you're not going to increase the amount of blood in your major arteries and veins. The amount of blood in them is fairly fixed (or is it?)

Rather, you'll increase the amount of blood in more peripheral blood vessels. How much does this amount of blood scale with increased mass? Is fat tissue more vascularized (on average) than other types of tissue? Or not? Furthermore, is it a valid assumption that a drug will diffuse "equally" throughout the body, including all of the body's capillaries?

Fluid spaces scale pretty dog-gone linearly with body size. There is a "standard" or "average" person for each group that calculations are done. For instance the "standard" male for age 17-34 is 70 Kg.

60% of the 70 Kg mass is fluid or 42 L. Of the 42 L, approximately 35-45% (40% avg) will be intracellular fluid (ICF) or 28 L.

Extracellular fluid (ECF)volume is 15-25% (20% avg) or approximately 14 L.

Of that (the ECF) approximately 5% is plasma (3.5 L) and approximately 15% is interstitial fluid (ISF) or 10.5 L.

For the given age group, these numbers make a very close approximation, so for the age group of 17-34 you can use these percents to calculate dosage when giving IV drugs or orals, etc. One must also consider things like the rate of clearance by the kidneys (weak acids and bases, like some drugs are (penicillin for example), are cleared rapidly by the kidneys unless given in excessive amounts).

Of course, there is variation in the population either through physiological variation or pathology, such as dehydration or edema etc. Which can alter the fluid spaces and must be something the prescribing physician takes into consideration.

MDs have these nice little charts and calculators for body size and drug prescribing, though most people fall within the bell curve and the averages can be use. Thankfully, this is something medical physiologists looked into :)

 

[bobze]

That is the intuitive way to generate the hypothesis. But we would also need to compare this value between different people - because thin people owe a greater proportion of their blood volume to their major blood vessels - whose volume cannot increase with body mass. It's entirely possible that it's a nonlinear function of body weight among adult individuals of a given height. (it's also entirely possible that the function could be non-linear for increases in height too, although I think this is less likely).

The size of vasculature and amount of whole blood volume in said vasculature also scales very well with body size.

 

[Simfish]

Fluid spaces scale pretty dog-gone linearly with body size. There is a "standard" or "average" person for each group that calculations are done. For instance the "standard" male for age 17-34 is 70 Kg.

60% of the 70 Kg mass is fluid or 42 L. Of the 42 L, approximately 35-45% (40% avg) will be intracellular fluid (ICF) or 28 L.

Extracellular fluid (ECF)volume is 15-25% (20% avg) or approximately 14 L.

Of that (the ECF) approximately 5% is plasma (3.5 L) and approximately 15% is interstitial fluid (ISF) or 10.5 L.

For the given age group, these numbers make a very close approximation, so for the age group of 17-34 you can use these percents to calculate dosage when giving IV drugs or orals, etc. One must also consider things like the rate of clearance by the kidneys (weak acids and bases, like some drugs are (penicillin for example), are cleared rapidly by the kidneys unless given in excessive amounts).

Of course, there is variation in the population either through physiological variation or pathology, such as dehydration or edema etc. Which can alter the fluid spaces and must be something the prescribing physician takes into consideration.

MDs have these nice little charts and calculators for body size and drug prescribing, though most people fall within the bell curve and the averages can be use. Thankfully, this is something medical physiologists looked into :)

Ah yes, thanks for this very nice reply! :)

 

[Andy Resnick]

Okay, basically, the more mass you have, the more drug that's needed to exert the same effect on you.

That's not true for all drugs- some psychoactive ones, in particular, do not have a dose-response that scales with body mass.

 

[SW VandeCarr]

Given the variety of drugs we have at our disposal, it's hard to generalize. Many drugs are water soluble, some are fat soluble, some cross the blood-brain barrier, some don't. Some are tissue bound, others protein bound, etc. A key concept is the volume of distribution which the relates the time integrated change in blood plasma levels from time t_{0} in a theoretical volume following the administration of known doses by known routes. This is affected by all the above variables (and more) plus rates of excretion, deposition in fat and bone and the production of metabolites which may or may not be measured in the plasma depending on whether they are active metabolites or not. The link below is a fair summary to just give a sense of the issues involved.

The recommendations for dosage by unit/kg are based on adjustments for these pharmacokinetic parameters, but prescribers must also estimate the fat/lean body mass ratios, level of hydration, renal and liver function, and other special situations that may exist. Dosages in children are also subject special guidelines.

http://www.merckmanuals.com/professional/sec20/ch303/ch303d.html

Note: multiple pages