RE: CrcL or Cr in pediatric model

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)