Back to the Top
I need to convert a human drug dose in mg/(meter squared) to a comparable
dose in rats. How does one calculate the surface area of a rat. Is there
a formula? In addition, how can the human dose be converted into a rat
dose on a mg/kg basis?
Back to the Top
Person to contact regaridng this issue is Dr. Harold Boxenbaum
Tel (301) 424-2806
Back to the Top
I do not know how to calculate the surface area of a rat! .... but I
think you don't need to.
I have always used the conversion 1 mg/kg = 6 mg/sq.m for rats.
(In mice 1 mg/kg = 3 mg/sq.m)
Therefore you should be able to work out an appropriate dose if you know
the mg/sq.m dose in man.
Hope this is helpful - others may disagree, it will be interesting to
see if there any other comments.
Duncan Jodrell
Edinburgh
Back to the Top
It depends upon the rat and the person. The questions you ask are
spelled out in:
Freireich EJ et al. Quantitative comparison of toxicity of anticancer
agents in mouse, rat, hamster, dog, monkey and man. Cancer Chemo
Reports 1966;50:219-244.
Another paper to look for is:
Monro A, and Mordenti J. Expression of exposure in negative
carcinogenticity studies: dose/body weight, dose/body surface are or
plasma concentrations? Toxicolgy Pathology 1995;23:187-98.
which has a comprehensive table describing physiological differences
between rats and humans to guide your allometric conversions.
Joan K-B
Back to the Top
A good reference to start with is 'First-time-in-human dose selection:
Allometric thoughts and perspectives, by Boxenbaum and Dilea,
J.Clin.Pharmacol. 35:957-966(1995).
Back to the Top
You could use pharmacokinetic-based approach to convert human dose to rat
dose using AUC or PBPK methods. These are outlined in a review written
by Voisin et al., entitled "Extrapolation of animal toxicity to humans:
interspecies comparisons in drug development" that appeared in Regulatory
Toxicology and Pharmacology. 12(2): 107-116, 1990 (October).
Rajesh Krishna
Back to the Top
Species Body Wt.(KG) Body Surf. Area (Sq. Mtr) Km Factor
Mouse 0.2 0.0066 3.0
Rat 0.15 0.025 5.9
Monkey 3.0 0.24 12
Dog 8.0 0.40 20
Human
Child 20.0 0.80 25
Adult 60.0 1.60 37
Ref: Freireich E.J. et.al. Cancer Chemother. Reports 1966, 50(4) 219-244.
Body Surface area dependent Dose conversion
Rat (150g) to Man (60 Kg) is 1/7 the rat dose
Dog (8Kg) to Human (60 Kg) is 1/2 the dog dose.
Hope this helps you,
Prasad Tata, Ph.D.
Otsuka America Pharmaceuticals Inc.
Back to the Top
Calculation of APPROXIMATE body surface area (BSA) uses simple
allometric relationship based on body weight (W):
BSA = W to the 0.67 power.
The Freireich data are reanalyzed (by allometric approach) in "Dosage
Regimen Design for Pharmaceutical Studies Conducted in Animals," J.
Mordenti, J. Pharm. Sci., 75:852-57, 1986. A good discussion on
allometry and tables of BSA data appear in "Extrapolation of
Toxicological and Pharmacological Data from Animals to Humans," W.
Chappell & J. Mordenti, Advances in Drug Research, Vol. 20, 1-116, 1991
(published by Academic Press Ltd).
- regards, Joyce
PS Joan, I was surprised by your plug for the Monro/Mordenti paper. I
didn't expect many pharmacokineticists to discover it. Thanks!
Back to the Top
>
> Calculation of APPROXIMATE body surface area (BSA) uses simple
> allometric relationship based on body weight (W):
>
> BSA = W to the 0.67 power.
>
But why use BSA in preference to more empirically sound allometric
models?
The only thing going for BSA is tradition. The usual Du Bois & Du Bois
model for BSA is based on 10 individuals. An allometric exponent of 3/4
instead of 2/3 is based on a multitude of observations across several
orders of magnitude of weight and varieties of animals.
See:
Peters RH. The ecological implications of body size. Cambridge:
Cambridge University Press, 1983
This is THE reference work for a wider view of allometrics.
Holford NHG A Size Standard for Pharmacokinetics Clin.
Pharmacokin. 1996;30:329-332
Compares common size models for clearance and shows the potential
weakness especially at low body weights e.g. children in comparison to
the 3/4 exponent model.
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, Private Bag 92019, Auckland, New Zealand
email:n.holford.at.auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556
http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.html
|
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@lists.ucdenver.edu with "Body surface area calculation" as the subject | Support PharmPK by considering my eBooks |
Copyright 1995-2014 David W. A. Bourne (david@boomer.org)