Re: [NMusers] Sparse (pediatric) and rich (adult) data

Chandra,

With such a small sample its hard to learn much about differences
between adults and children. Your principled approach using allometric
scaling is a reasonable way to bridge the gap in recognizing that adults
and children are all the same species (see reference below).

"Children are just small adults"

I would not be too worried about individual parameter estimate in
children being different. With only 3 samples per child and a 2 cmt
model requiring at least 4 parameters you will always get different
results if you use different assumptions.

Nick

Anderson BJ, Holford NH. Mechanism-Based Concepts of Size and Maturity
in Pharmacokinetics. Annu Rev Pharmacol Toxicol. 2008;48:303-32.


Chandrasekhar Udata wrote:
> Hi,
>
> I am working on a pop PK model to estimate PK parameters in pediatric
> and adult patients. Pediatric study (n=20, age <6 yrs) has fewer
> samples (3) per subject whereas the adult study (n=50, median age 20
> yrs) has 12 samples per subject. A two-compartment model best
> describes the data for each data set. Although a two-compartment model
> best describes the combined data, the individual parameter estimates
> in pediatric population are different compared to those obtained
> using with pediatric data alone. Note that the parameter estimates in
> adults were not significantly altered with either combined or adult
> data alone. Body weight is the only covariate included in the model
> with allometric exponents fixed to 0.75 on CL and 1 on V1.
>
> I would like to hear your thoughts on this and any suggestions on how
> to proceed with modeling combined data from pediatric and adult studies.
>
> Regards,
> - Chandra
>

--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
n.holford_at_auckland.ac.nz tel:+64(9)373-7599x86730 fax:+64(9)373-7090
www.health.auckland.ac.nz/pharmacology/staff/nholford


Received on Wed May 28 2008 - 13:38:07 EDT