Don't know about Evans Blue, but here are a lot of "goodies" aboutBack to the Top
blood volume, etc. Enjoy! Harold
Species\0xED Body Masses (kg), Gut Volumes (mL) & Maximum Drug Solubility
in Species\0xED Guts. Gut Mass and Volume Data from Davies & Morris,
Species Mass Gut Mass
Mouse 0.02 kg 1.5 mL
Rat: 0.25 kg 11.3 mL
Rabbit: 2.5 kg 120 mL
Monkey: 5 kg 125 mL
Dog: 10 kg 215 mL
Human: 70 kg 1100 mL
Jennifer Dressman has suggested (personal communication) that a
'rule-of-thumb' to evaluate whether or not a dose of drug will
completely dissolve in the human gut, is to take the dose and determine
if it is capable of dissolving in 500 mL water. Five hundred mL water
is 45.5 % of the human gut volume, so we might apply this percentage to
other species. In doing so, we obtain the following for other species:
Mouse 0.68 mL
Rat 5.1 mL
Rabbit 55 mL
Monkey 57 mL
Dog 98 mL
Human 500 mL
For example, is a drug has a water solubility of 1 mg/mL, and we
administer more than 5.1 mg to a rat, we will likely have undissolved
drug passing through the GUT. In this case, look for 'flip-flop'
Interspecies Body Surface Area
Many laboratory scientists utilize Appendix II in the publication by
Freireich et al (1966) to calculate species body surface area (BSA).
Unfortunately, the data upon which this approach is based is
considerably unreliable. Therefore, it is recommended you do not use
this method. Rather, body surface area in all terrestrial mammals may
be accurately estimated by utilizing the simple allometric equation
(Calder, 1984; Boxenbaum & D\0xEDSouza, 1990; Stahl, 1967) :
BSA (m^2) = 0.1110 B (kg) ^ 0.65
A 3 gram shrew has a BSA of 0.848 m2/kg, compared to 0.0251 m2/kg for a
human. Based on body mass, the shrew has 34 times the surface area of
the human. Consequently, a shrew requires much more food intake per kg
body mass to compensate for radiant heat loss across its significantly
larger, relative body surface area. An animal deprived of food for 2-3
hours could easily die (Burton and Burton, 1975).
For possibly the best discussion of body surface surface area, as well
other variables for interspecies biological extrapolation, see Chappell
and Mordenti (1991).
Human Body Surface Area
In 1916, Du Bois & Du Bois published an equation for calculation of
body surface area (BSA) in humans, based on a sample size of 9
individuals. That equation is (appropriately adjusted for units):
BSA (m^2) = 0.007184 x [(Height, cm) ^ 0.725] x (Body
Mass, kg) ^ 0.425
Using a much larger sample size, Gehan and George (1970) obtained the
following analogous equation:
BSA (m^2) = 0.02350 x [(Height, cm) ^ 0.42246] x
[(Body Mass, kg) ^ 0.51456]
Although the equation of Du Bois & Du Bois is frequently used in
clinical trials for calculation of BSA, it is less accurate than the
equation of Gehan and George. Nonetheless, scientists sometimes
continue to use the Du Bois & Du Bois equation for the sake of
consistency between previous studies which previously employed the
DuBois n DuBois equation.
Terrestrial Mammals\0xED Hematocrit & Blood and Plasma Volume
Blood volume (mL) = 0.086 (B, grams) ^ 0.99 or about 8.6 % of body
Red blood cell volume (mL) = 0.036 (B, grams) ^ 0.97
Dividing the equation for RBC volume by blood volume, one obtains
hematocrit. Hematocrit (H) therefore equals H = 0.4186 (B, grams)
-0.02 or about 0.4 for all terrestrial mammals
Plasma volume = blood volume x (1- hematocrit), or about 5.2 % of
Human Hepatic Blood Flow (QH)
Greenway & Stark (1971) surveyed the literature and determined the best
value for human hepatic blood flow to be 104 mL/min per 100 grams of
liver mass. Taking the human male liver mass to be 1800 grams (Snyder,
chair, Report of the Task Group on Reference Man, 1975), one obtains
the following for male, human hepatic blood flow:
(104 mL/min per 100 grams liver mass) x (1800 grams) = 1872
Taking the male body mass to be 70 kg, QH (human male) = (1872
For the female, the average liver mass = 1400 grams in an average 58 kg
body. QH (human female) = (104 mL/min per 100 grams liver mass)
x (1400 grams) / (58 kg body mass)
= 25.1 mL/min/kg. A generalized value might therefore be about 25
Lean Body Mass (LBM) Calculation
Lean body mass equals total body mass minus fat mass.
Without going into its history, which involves a very hard-to-get
reference with vagaries, typographical errors, etc., one may reliably
calculate lean body mass (total body mass minus fat mass) from the
following two equations (Morgan & Bray, 1994: there were typographical
errors in equation 1 of this reference which were corrected in the
equations listed below)
LBM (men) = [1.10 B ] n [ 128 (B/Ht)^2 ]
LBM (women)= [1.07 B ] n [ 148 (B/Ht)^2 ]
where B is body mass in kg, and Ht is height in cm.
For a 70 kg male having a height of 166 cm,
LBM = [1.10 x 70 ] n [ 128 (70/166)^2 ] = 77.00 n 22.76 = 54.24
Body Mass Index
'A number of methods are used to determine if someone is overweight or
obese. Some are based on the relation between height and weight; others
are based on measurements of body fat. The most commonly used method
today is body mass index (BMI).
BMI can be used to screen for both overweight and obesity in adults. It
is the measurement of choice for many obesity researchers and other
health professionals, as well as the definition used in most published
information on overweight and obesity. BMI is a calculation based on
height and weight, and it is not gender-specific. BMI does not directly
measure percent of body fat, but it is a more accurate indicator of
overweight and obesity than relying on weight alone.
BMI is found by dividing a person\0xEDs weight in kilograms by height in
meters squared. The mathematical formula is:
BMI = Weight (kg) / Height Squared (m^2)
To determine BMI using pounds and inches, multiply your weight in
pounds by 704.5,* then divide the result by your height in inches, and
divide that result by your height in inches a second time. (Or you can
use the BMI calculator at http://www.nhlbisupport.com/bmi/ or check the
chart shown below that has calculated BMI for you.)'
Underweight: Below 18.5
Normal: 18.5 n 24.9
Overweight: 25.0 n 29.9
Obesity: 30.0 and Above (e.g., B=101
kg, Ht = 165 cm; BMI = 37.1)
Harold Boxenbaum, Ph.D.
14621 Settlers Landing Way
North Potomac, MD 20878-4305
Back to the Top
Here are the missing references, plus some extra I did not have time to
cull out. Harold
Bonate PL, Howard D, Prospective allometric scaling: does the emperor
have cloths? J Clin Pharmacol 40:335-340 (2000)
Bonate PL, Howard H, Rebuttal to Mahmood, J Clin Pharmacol 40:345-346
Boxenbaum H, Interspecies variation liver weight, hepatic blood flow,
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benzodiazepines and phenytoin. J. Pharmacokin. Biopharm. 8:165-176
Boxenbaum, H, Interspecies scaling, allometry, physiological time, and
the ground plan of pharmacokinetics. J. Pharmacokin. Biopharm.
Boxenbaum H, 'Interspecies pharmacokinetic scaling: Desultory
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Library Series, International Business Communications, Inc,
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Boxenbaum H, DiLea C, First-time-in-human dose selection: Allometric
thoughts and perspectives, J Clin Pharmacol 35:957-966(1995).
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Calder III WA. 'Size, Function, and Life History,' Harvard Univ Press,
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Cephalopoda Cuvier, 1797:
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Harold Boxenbaum, Ph.D.
14621 Settlers Landing Way
North Potomac, MD 20878-4305
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (email@example.com)