Pete,
Is the drug cleared almost completely thru renal elimination?
Otherwise, maybe a slope intercept model for CL as a function of CRCL?
TVCL=THETA(X)*(WT/70)**0.75+THETA(Y)*CRCL
The intercept is nonrenal CL according to the allometric model and the
slope according to CRCL. This model may be inappropriate if renally
impared are included in the dataset or if there are other reasons to why
the linear model for CRCL may be inappropriate. With this model the
collinearity is a smaller problem since the exponent in the allometric
model is not estimated.
Best regards
Jakob
________________________________
From: owner-nmusers
On Behalf Of Bonate, Peter
Sent: 12 January 2009 21:52
To: nmusers
Subject: [NMusers] CrcL or Cr in pediatric model
I have an interesting question I'd like to get the group's collective
opinion on. I am fitting a pediatric and adult pk dataset. I have
fixed weight a priori to its allometric exponents in the model. When I
test serum creatinine and estimated creatinine clearance equation as
covariates in the model (power function), both are statistically
significant. CrCL appears to be a better predictor than serum Cr (LRT =
=
22.7 vs 16.7). I have an issue with using CrCL as a predictor in the
model since it's estimate is based on weight and weight is already in
the model. Also, there might be collinearity issues with CrCL and
weight in the same model, even though they are both significant. Does
anyone have a good argument for using CrCL in the model instead of serum
Cr?
Thanks
Pete bonate
Peter L. Bonate, PhD, FCP
Genzyme Corporation
Senior Director
Clinical Pharmacology and Pharmacokinetics
4545 Horizon Hill Blvd
San Antonio, TX 78229 USA
peter.bonate
phone: 210-949-8662
fax: 210-949-8219
crackberry: 210-315-2713
alea jacta est - The die is cast.
Julius Caesar
Received on Mon Jan 12 2009 - 17:38:08 EST
