Winnie
If the age and weight ranges are large enough, you may apply an allometric
rule to the PK parameters that relate to dosing, volumes and CL :
CL = TVCL*BW**(power CL)
and
V = TVV*BW**(power Vd)
1.You may fix the exponents, powerCL and powerVd to 0.75 and 1 respectively
or try to estimate them with your data.
2. If the CL and Vd exponents are fixed, you may try to estimate an age
effect, provided very young children data are available.
You will find extensive details and references in the paper
Anderson et al (2006) Vancomycin PK in preterm neonates and the prediction
of adult clearance. Br J Clin Pharmacol vol 63, p.75-84
Saik
Dr Saik URIEN
Directeur de Recherche à l' INSERM
Unité de Recherche Clinique (URC)
HOPITAL TARNIER
89 rue d'Assas
F75006 PARIS
01 5841 2880
Email : [EMAIL PROTECTED]
Quoted reply history
----- Original Message -----
From: <[EMAIL PROTECTED]>
To: <[email protected]>
Sent: Tuesday, March 25, 2008 6:26 PM
Subject: [NMusers] Re: [NMUSERS] Questions on fitting pediatric PK data
using NONMEM
>
> 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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