NONMEM Users Network Archive

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RE: CrcL or Cr in pediatric model

From: Ribbing, Jakob <Jakob.Ribbing>
Date: Wed, 14 Jan 2009 09:10:48 -0000

Leonid,

As I understand the linear model you suggested it can be simplified* to
this structure:
THETA(1)*((WT/70)^(3/4)+THETA(2)*CRCL)

I call this additive, because the two covariates affect TVCL in an
absolute sense, without interaction. My main message was that I find
this model appealing, because it has the properties:
a)There is a linear increase of CL with CRCL
b)An increase in CRCL increases CL with an absolute number which is the
same for two subjects with different WT

The same can not be said about this model:
TVCL=THETA(1)*(WT/70)^(3/4) * RF^GAMMA
The latter model carries a built-in interaction which may provide a
better description of the data in situations where e.g. non-renal
elimination decreases with CRCL or where the secretory component of
renal elimination is more important for creatinine than for the drug.
However, in the opposite situations the interaction would be working in
the wrong direction (assuming GAMMA<1). Maybe we can leave what
basic-model assumption we want to use as a matter of personal or
drug-specific preference?

Best

Jakob

PS
Nonmem users is like an octopus: Just when you think you are free one of
its threads pulls you back in again :>)
Much of this discussion is around additivity. If I have understood the
definition of additivity wrong, then I apologies on beforehand, so that
this can still be my final "contribution" to this thread. Likewise if I
misunderstood what model Leonid was actually suggesting...
DS

*This is how I have simplified the suggested linear model:
TVCL=THETA(1)*(WT/70)^(3/4) * (1+THETA(2)*RF)=
    =THETA(1)*(WT/70)^(3/4) * (1+THETA(2)*CRCL/(WT/70)^(3/4)) =
=THETA(1)*(WT/70)^(3/4)+THETA(1)*(WT/70)^(3/4)*THETA(2)*CRCL/(WT/70)^(3=
/
4)=
    =THETA(1)*((WT/70)^(3/4)+THETA(2)*CRCL)

Or =THETA(1)* (WT/70)^(3/4)+THETA(1)*THETA(2)*CRCL
Similar: THETA(1)* (WT/70)^(3/4)+THETA(2)*CRCL (where the interpretation
of THETA(2) changed from the line before)

-----Original Message-----
From: owner-nmusers
On Behalf Of Leonid Gibiansky
Sent: 13 January 2009 22:50
To: nmusers
Subject: Re: [NMusers] CrcL or Cr in pediatric model

Jakob,

The model that I mentioned is not additive; it is multiplicative:

Parameter= MeanValue*Effect1(WT)*Effect2(RF)

but the effect of RF is expressed as a linear function of RF
Effect2(RF) = 1 + THETA()*RF

Leonid




 
Received on Wed Jan 14 2009 - 04:10:48 EST

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