Back to the Top
Dear friends,
Usually, a drug is dosed per kilo bodyweight in
children and the recommended dose per kilo may vary between different age
groups (depending on different pharmacokinetics/dynamics in the age
groups). What is the rationale for not dosing just by age? Is it likely
that a big 2 year-old will have higher hepatic or renal clearance than a
small 2 year-old? That is - is weight and organ function correlated within
the same age?
Do anyone have some knowledge about this?
I would be very grateful.
Eva Rasmussen
Dept of Clinical Pharmacology
University Hospital
S-751 85 Uppsala
SWEDEN
mail: Eva.Rasmussen.-at-.klinfarm.uu.se
Back to the Top
[A few replies - db]
From: "Jones, Jim - Pharm Tox"
To: "'PharmPK.-at-.pharm.cpb.uokhsc.edu'"
Subject: RE: PharmPK Dosing in children
Date: Fri, 23 Oct 1998 15:44:44 -0400
X-Priority: 3
MIME-Version: 1.0
Within each age there is a standard deviation about the mean of weights.
Some kids are malnourished were others (especially here in the U.S.) are
quite fat for the same age. This difference in weight may be quite
significant (20 to 50 Kg. in adolescents). It is easier to dose based on
weight for this reason.
Jim Jones, Pharm.D.
Columbus Children's Hospital
Section of Pharmacology and Toxicology
Pediatric Pharmacology Research Unit
---
Reply-To:
From: "Eric Masson"
To:
Subject: RE: PharmPK Dosing in children
Date: Fri, 23 Oct 1998 16:31:59 -0400
MIME-Version: 1.0
X-Priority: 3 (Normal)
Importance: Normal
It is usually better to adjust per body surface area than body weight. Body
surface area is usually better correlated with physiologic function (e.g.
GFR, hepatic flow) than body weight. The only exception is for intrathecal
doses since CSF volume does not correlate with BSA. IN that case,
intrathecal doses are usually adjusted per age up to 2 years, with a fixed
dose from 2 years and older (even adult). However, ajusting per body weight
or body surface area within the same age group or within adult probably is
probably not necessary. Try for some data set and you'll see that it make
little difference unless you have obese patients.
=C9ric Masson, Pharm. D.
Scientific Director,
Anapharm Inc.
2050 boul. Rene-Levesque Ouest, 5e etage
Ste-Foy, QC, Canada, G1V-2K8
tel: (418) 527-4000
telec: (418) 527-3456
email: emasson.-a-.anapharm.com
---
From: HRr1234.-a-.aol.com
Date: Fri, 23 Oct 1998 18:01:24 EDT
To: PharmPK.aaa.pharm.cpb.uokhsc.edu
Mime-Version: 1.0
Subject: Re: PharmPK Dosing in children
Chapter 10 in the 3rd edition of Applied Therapeutics, Principles of
Therapeutic Drug Monitoring, edited by Wm Evans, J Schentag, & Wm Jusko;
Applied Therapeutics, Vancouver, WA, 360-253-7123, gives extensive info
reagrding this subject.
Back to the Top
[Two more replies - db]
From: "Nick Holford"
To:
Subject: Re: PharmPK Re: Dosing in children
Date: Tue, 27 Oct 1998 20:53:40 +0200
MIME-Version: 1.0
X-Priority: 3
My own reading of the literature and a little experience of the problem
suggests an allometric model with wt**3/4 is better than BSA on empirical
grounds. BSA *is* better than per kg (i.e. wt**1) for clearance but still
not as good as wt**3/4.
Anderson BJ, McKee D, Holford NHG. Size, myths and the clinical
pharmacokinetics of analgesia in paediatric patients. Clinical
Pharmacokinetics 1997; 33:313-327
Holford NHG. A size standard for pharmacokinetics. Clin. Pharmacokin. 1996:
30:329-332
> The only exception is for intrathecal
> doses since CSF volume does not correlate with BSA.
Not surprising. Allometric observation suggests structural properties such
as volume are linearly related to weight so power functions such as BSA
(approx wt**2/3) do not do so well.
--
Nick Holford
Dept Experimental & Clinical Pharmacology
University of Natal Medical School, Durban, South Africa
n.holford.-at-.auckland.ac.nz
---
From: "Boos, Joachim"
To: "'PharmPK.-at-.pharm.cpb.uokhsc.edu'"
Subject: AW: PharmPK Re: Dosing in children
Date: Wed, 28 Oct 1998 13:37:44 +0100
MIME-Version: 1.0
The problem of dosing in children is much too complex for short statements.
BW-based dosages calculated from adult standards normaly result in much to
low exposure. BSA parallels much better the total body water and the
extracellular body water and as well "metabolism".
But is this really relevant? Maturation of kidney function and hepatic
metabolism does not parallel development of weight and height. Most drugs
are not solely distributed into extracellular water compartments, fat
composition depends on age and nutrition and the percent fat increases and
decreases within the first years of life.
In the discussion of BW and BSA the historical arguments are quiet
interesting as in summary, for most of todays practical therapeutic
decisions, they are not relevant or missing. For cytostatic drugs, normally
dosed by BSA, a comparison of "usual effective dosages" in different
animal systems and man provides the basis for the general regimen.
For single drugs the half-life and volume of distribution may be longer as
well as shorter (higher/lower) in infants and children during their
development (for example theophyllin, cefotaxim). The only rational
solution, therefore, is to dose drugs on the basis of their pharmacokinetic
and -dynamik properties with respect to the childs state of development and
not on more or less simple sqm or kg rules.
A higher extracelluar space may in a newborn or infant be an argument for
relatively higher dosage of drugs beeing solely distributed in this
compartment. If its excretion is simply glomerular filtration, the half
life will be prolonged and this should result in reduction of dose
intensity. For this examplary drug (gentamycin, vancomycin may be one) the
single dose might be increased, the interval has to be prolonged.
For everybody who is in doubt: look for standard dosages for infants in any
textbook and calculate your personal dose (based on your BW or BSA). Would
you really take that amount?
Unfortunatly, the idea of pharmacokinetically based dose calculation needs
much more data and informations than we have. The best way for dosing in
children today is, therefore, to look in empirical based data sets. For new
drugs, however, pharmacokinetics and dose schedules for children should be
investigated as early as possible during drug development.
J Boos
Dept. of Pediatr. Hematol/Oncol
Univ. M=FCnster
FRG
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)