drug discovery

INTER-CONVERSION OF DRUG DOSAGE BETWEEN SEVERAL SPECIES DURING DRUG DEVELOPMENT
By AWAH FAVOUR ([email protected])
During drug development, other species other than man are used for trials and determination of safety limits for a given drug. It becomes necessary to convert the dosage from one specie to another. Since these animals have different body surface area and average body weight, it is necessary to use conversion factors.
Equivalent Surface Area Dosage Conversion Factors
TO

FROM
Mouse 20 g
Rat 150 g
Monkey 3 kg
Dog 8 kg
Man 60 kg

Mouse
1
1/2
1/4
1/6
1/12

Rat
2
1
1/2
1/4
1/7

Monkey
4
2
1
3/5
1/3

Dog
6
4
1 2/3
1
1/2

Man
12
7
3
2
1

This table provides the approximate factors for converting doses expressed in terms of mg/kg from one species to an equivalent surface area dose expressed as mg/kg in the other species.
Also, after animal studies, safety limits are usually expressed in mg/kg .sometimes for more effective application of experimental findings it is necessary to convert to other unit of measurement. To do this, a representative surface area to weight ratio (KM) is needed.
Representative Surface Area to Weight Ratios [km] for Various Species
Species
Body Weight [kg]
Surface Area [sq. m.]
km factor

Mouse
0.02
0.0066
3.0

Rat
0.15
0.025
5.9

Monkey
3.0
0.24
12

Dog
8.0
0.40
20

Human, pediatrics
20
0.80
25

Human, Adult
60
1.6
37

Exercise: Animal studies by sweet reveal that the safety dose for doxorubicin is 1.54mg/kg -1.74mg/kg. Calculate the equivalent dose for human adults in mg/m2 if she used albino rats.

Solution: convert from rat to man (1.54 ÷1/7) and (1.74 ÷1/7) = 10.81 mg/kg to 12.16mg/kg
Next, convert from mg/kg to mg/m2: (10.81x37) and (1.74x37) = 400mg/m2- 450mg/m2
Thus the safety limits for doxorubicin is 400mg/m2- 450mg/m2. The dose at which it will manage cancer with no significant cardiomyopathy.