# RE: Phsysiological model

From: Eleveld, DJ <d.j.eleveld>
Date: Tue, 6 Oct 2015 08:30:03 +0000

Hi Andre,

Hopefully you can see that
(1) QCO=15.87*(BW)**0.75
calculates very different values for QCO compared to
(2) QCO=15.87*(WT/WTstd)**0.75
unless of course WTstd is 1kg. In that case (WTstd is 1 kg) then they are e=
xactly the same.

The easiest way to separate these situations is to find out the units of th=
e 15.87. Where does this number come from?
If QCO is cardiac output (i am just guessing here) then the units should be=
l/min or something like that. In (1) the 15.87 is the l/min/kg
but in (2) the units of the 15.87 are l/min/70kg. So for (1) a 70 kg person=
QCO would be 384 l/min while for (2) a 70 kg persom gives 15.87 l/min.
Hopefully one of these is obviously wrong so you can pick the right one.

If the 15.87 is an estimated parameter (a THETA) then it does not matter (i=
n a mathematical functional sense) what WTstd you use. It does the change t=
he units of the THETA you estimate.
Using 1 kg seems mathematically easiest but it makes interpretation a bit h=
arder. The advantage of using WGTstd=70kg is that the estimated THETA has=
an easy interpretation as the predicted QCO for a standard individual. Thi=
s makes comparison between studies quite a bit easier.
A simplified example for an imaginary drug:
Imagine studies in children and adults and obese and they all normalize to =
their median weights in thier individual studies so for clearance they migh=
t find something like:
(children) CL=0.314*(WT/15kg)**0.75
(obese) CL=1.498*(WT/120kg)**0.75
Do these look different from each other? Superficially they do. But if you =
use the adult equation to calculate the values for children and obese you g=
et:
(adult formula, predict 15 kg child)CL=1*(15kg/70kg)=0.314
(adult formula, predict 120 kg obese)CL=1*(120kg/70kg)=1.498
So the three formulas (children,adults,obese) are actually exaclty the same=
because they predict the same CL values for all weights. This is the advan=
tage for using WTstd=70kg even if the median weight isnt close to 70 kg.

I agree with Nich Holford about the theoretical scaling exponent for k valu=
es. If you are estimating values where the units are 1/time then the scalin=
g exponent should be -0.25.

warm regards,
Douglas Eleveld

________________________________
Van: owner-nmusers
ens Andre Jackson
Verzonden: October 5, 2015 7:18 PM
Aan: nmusers
Onderwerp: [NMusers] Phsysiological model

All:

I am attempting to take a Physiological model presented in the literature a=
nd place it into Nonmem with the help of the authors. A point was raised =
related to centering parameters which I would appreciate some feedback.

In the published paper, model parameters such as Cardiac output are allomet=
rically scaled as power models:
QCO=15.87*(BW)**0.75
and gut metabolism as:
K_Gutmet=THETA(2)*(WT)**0.75)

My question is should I use these equations as stated in the publication or=
should I center the estimates as e.g.,
QCO=15.87*(WT/WTstd)**0.75

The weights that will be investigated go from 30 kg up to 80 kg.

It would also be very helpful if one can give me an explanation as to why o=
r why not.

Thanks
Andre

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Received on Tue Oct 06 2015 - 04:30:03 EDT

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