Re: Scaling of pharmacokinetics in peds
From: Nick Holford - n.holford@auckland.ac.nz
Subject: Re: [NMusers] Scaling of pharmacokinetics in peds
Date: 12/17/2003 3:22 PM
Peter,
I don't know who is the advocate for an allometric exponent of 0.7
for clearance. I do not wish to be counted among the "everyone
[who] pretty much agreed" to a value of .7
Here (again) are some references for theory and experiment in
support of a value of 0.75.
Peters R.
The ecological implications of body size.
Cambridge: Cambridge University Press; 1983.
West GB, Brown JH, Enquist BJ.
A general model for the origin of allometric scaling laws in biology.
Science 1997;276:122-26.
West GB, Brown JH, Enquist BJ.
The fourth dimension of life: fractal geometry and allometric scaling of organisms.
Science 1999;284(5420):1677-9.
Anderson BJ, van Lingen RA, Hansen TG, Lin YC, Holford NHG.
Acetaminophen developmental pharmacokinetics in premature neonates and infants: a pooled population analysis.
Anesthesiology 2002;96(6):1336-45.
This is a useful page explaining some background to allometric ideas:
http://www.anaesthetist.com/physiol/basics/scaling/Kleiber.htm
At any given conc then CL is
Vmax
CL = ----------
Km + Conc
It can be allometrically scaled as follows:
VmaxStd
CLStd*Fsize = (---------)*Fize
Km + Conc
where Fsize=(WT/WTstd)**0.75
No allometric scaling would be expected a priori on Km. So I think it
might be reasonable to restate this expression as:
VmaxStd*Fsize
CLStd*Fsize = -------------
Km + Conc
i.e. apply the allometric scaling directly to Vmax alone.
Note, factors other than size (such as age) may be associated with between
subject differences in Km. It is important to recognize that size scaling
is not the only factor that explains between and within species differences.
These other factors may sometimes obscure the view of what the emperor is wearing
Bonate PL, Howard D.
Prospective allometric scaling: does the emperor have clothes?
J Clin Pharmacol 2000;40(6):665-70; discussion 671-6.
Nick
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/