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
[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:+64(9)373-7090
www.health.auckland.ac.nz/pharmacology/staff/nholford
