Re: [NMusers] Re: [NMUSERS] Questions on fitting pediatric PK data using NONMEM

Winnie,

If you are serious about modelling PK in children then I suggest you
become familiar with some basic concepts of scaling for size and
maturational changes with age (see Anderson & Holford 2008). These can
be readily implemented in NONMEM.

In preparing your data the important thing is to record the actual dose
-- not the dose scaled per kg or per sq m. You should also try to get
body weight and height and post-menstrual age if you are dealing with
neonates.

Nick

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


winnie.seto_at_sickkids.ca wrote:
> Hello all
>
> I work with small number of pediatric inpatients with few samples from each
> patient of various age and weights.
>
> I am a novice in using NONMEM.
>
> I would appreciate advice on fitting the data using various dose inputs -
> should we normalize
> the dose and other parameters by weights ? Since the range is large
> in my datasets, the variability could be quite large without using /kg
> dosing.
>
> Example
> 24 patients with different age and size (paediatrics) on Cyclosporin IV
> infusion over 2 hours
> with 5 levels taken at similar times post 1st (and only dose). Although
> dose at 1.5mg/kg,
> the actual amount of dose given for each patient varies. Looking at the raw
> data and log conc vs time graphs,
> it appeared 2-compartment would be suitable. However, Volume of
> distributions and clearances
> varies with units without normalization to body weight (kg) or body size
> (BSA).
>
> Any thoughts or suggestions would be much appreciated.
> Thank You!
>
> Winnie
>
>
> Winnie Seto, BScPhm, PharmD, MSc, ACPR, R.Ph.
> Therapeutic Drug Monitoring Coordinator &
> Critical Care Unit Pharmacist
> The Hospital for Sick Children
> 555 University Avenue
> Toronto, Ontario
> Canada M5G 1X8
> phone: 416-813-6236
> fax: 416-813-5880
>
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>

--
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 Mar 26 2008 - 10:54:49 EDT