Thank you Nick and Leonid for your comments. Follow-up question: I do understand that 3 samples per subject may not support 4 parameters model. However, historically, the compound showed bi-phasic characteristics (in adults) and I do like to use the same model in pediatrics. Also, the model (ADVAN3, TRANS4) did converge with no issues/errors (with pediatric data alone). Is there something I am missing? or is TRANS5 (AOB, ALPHA, BETA) an alternative for such limited data? Regards, - Chandra
>>> Nick Holford <[EMAIL PROTECTED]> 5/28/2008 1:38:07 PM >>> 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
