This ratio method uses an established dosage in a specific species and links the
dosage to a physiological function instead of the animal’s body weight (Dorrestein
2000 ; Jacobson 1996 ; Morris 1999 ; Mortenson 2001 ; Sedgwick 1993 ; Sedgwick
and Borkowski 1996 ). This calculation forces an allometric (log–log) relationship,
usually with an exponent of 0.6–0.8 (Jacobson 1996 ; Morris 1999 ; Singer 2001 ).
The assumption is that, because most physiological functions follow allometric
equations relative to body weight (Kleiber 1932 , 1961 ), pharmacological para-
meters (Vdand Clp) will also follow similar allometric relationships.
This method of dose extrapolation using basal metabolic rate ratios provides a
relatively smaller dose for a large animal and a higher dose for a small animal, thus
solving one of the important problems associated with using linear extrapolations.
The basal metabolism method was established by and is commonly used in zoolog-
ical medicine. Practical descriptions of this method and the calculations used to
arrive at an extrapolated dose have been described by Sedgwick ( 1993 ) and others
(Dorrestein 2000 ; Jacobson 1996 ; Morris 1999 ; Mortenson 2001 ; Sedgwick and
Borkowski 1996 ). Briefly, all species are placed in one of five groups, termed
Hainsworth’s energy groups: passerine birds, nonpasserine birds, placental mam-
mals, marsupial mammals and reptiles. The species group is used to select a
predeterminedKvalue, which is a constant for each of the five Hainsworth energy
groups (Sedgwick 1993 ). TheKvalue is used to calculate the metabolic rate for the
selected species. A specific minimum energy cost (SMEC) value is calculated for
each species, and the ratio of the target species SMEC to the SMEC of a safe,
effective dose in a known species is calculated to derive an appropriate treatment
regimen (Dorrestein 2000 ; Jacobson 1996 ; Morris 1999 ; Mortenson 2001 ; Sedgwick
1993 ; Sedgwick and Borkowski 1996 ). This method is simple in that the basal
metabolic rate can be estimated for most species and applied to any pharmacological
agent. It also facilitates extrapolation from mammalian species to avian or reptile
species. Sedgwick’s dosage extrapolation method has been used to establish a dose
for conducting pharmacokinetic studies in new species (Downes 2002 ; Jacobson
1996 ). A commercially available computer program based on Sedgwick’s methods
has been distributed and used for dosage calculations (Gamble et al. 1995 ). An
example of Sedgwick’s method for the cephalosporin ceftizoxime is as follows:
Control species: mouse (Weight [Wkg] 0.023 kg)
Dose rate is 88 mg/kg every 1.2 h
SMEC¼KWkg^0 :^25¼ 179
SMEC dose is the dose rate divided by SMEC = 88/179 = 0.5
SMEC dose = 0.5
Frequency (number of treatment intervals per 24 h) = 24/1.2 = 20
SMEC frequency is the frequency divided bySMEC= 10/179 = 0.1
SMEC frequency = 0.1
This provides the veterinarian with the SMEC dose and frequency adjustment.
Illustrations of this approach for four species are as follows:
Interspecies Allometric Scaling 145