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Dose conversion

Safe and effective drug dosing is necessary, regardless of its purpose of administration. Allometric scaling is an empirical approach where the exchange of drug dose is based on normalization of dose to body surface area. This approach assumes that there are some unique characteristics on anatomical, physiological, and biochemical process among species, and the possible difference in pharmacokinetics/physiological time is accounted by allometric scaling. This method is frequently used in research for experimental purpose to predict an approximate dose on the basis of data existing in other species. The US Food and Drug Administration's current guidance is based on dose by factor approach where the NOAEL of drug is scaled by making use of allometry to derive the maximum recommended starting dose (MRSD) for clinical studies.

Usually the correction factor (Km) is used to estimate the animal equivalent dose (AED) for different animal species. Km is estimated by dividing the average body weight (kg) of species to its body surface area (m2). For example, the average human body weight is 60 kg, and the body surface area is 1.62 m2. Therefore, the Km factor for human is calculated by dividing 60 by 1.62, which is 37. As the Km factor for each species is constant, the Km ratio is used to simplify calculations. AED can be estimated as: AED1 (mg/kg) = AED2 (mg/kg) × Km ratio (Km2/Km1) Eq.1; or AED1 (mg/kg) = AED2 (mg/kg) × Weight2 (kg) × BSA ratio (BSA1/BSA2) Eq.2.

Species Reference body weight (kg) To convert dose in mg/kg to dose in mg/m2, divide by km To convert human dose in mg/kg to AED in mg/kg,either
Multiply human dose by Multiply human dose by
Mouse 0.02 3 12.3 0.081
Hamster 0.08 5 7.4 0.135
Rat 0.15 6 6.2 0.162
Ferret 0.3 7 5.3 0.189
Guinea Pig 0.4 8 4.6 0.216
Rabbit 1.8 12 3.1 0.324
Cat 2 11.7 3.2 0.316
Monkey 3 12 3.1 0.324
Dog 10 20 1.9 0.541
Marmoset 0.35 6 6.2 0.162
Squireel Monkey 0.6 7 5.3 0.189
Baboon 12 20 1.9 0.541
Micro pig 12 27 1.4 0.73
Mini pig 40 35 1.1 0.946
Human 60 37 1 1
Table 1. Animal equivalent dose calculation based on Km ratio.
A B Mouse
(20g)
Hamster
(80g)
Rat
(150g)
Ferret
(300g)
Guinea Pig
(400g)
Rabbit
(1.8kg)
Cat
(2.0kg)
Monkey
(3.0kg)
Dog
(10kg)
Human
(60kg)
Mouse (20g) 1.00 1.67 2.0 2.3 2.7 4.0 3.9 4.0 6.7 12.3
Hamster (80g) 0.60 1.00 1.20 1.40 1.60 2.4 2.3 2.4 4.0 7.4
Rat (150g) 0.50 0.83 1.00 1.17 1.33 2.0 1.95 2.0 3.3 6.2
Ferret (300g) 0.429 0.71 0.86 1.00 1.14 1.71 1.67 1.71 2.9 5.3
Guinea Pig (400g) 0.375 0.63 0.75 0.88 1.00 1.50 1.46 1.50 2.5 4.6
Rabbit (1.8kg) 0.250 0.417 0.50 0.58 0.67 1.00 0.98 1.00 1.67 3.1
Cat (2.0kg) 0.256 0.427 0.51 0.60 0.68 1.03 1.00 1.03 1.71 3.2
Monkey (3.0kg) 0.250 0.417 0.50 0.58 0.67 1.00 0.98 1.00 1.67 3.1
Dog (10kg) 0.150 0.250 0.300 0.350 0.400 0.60 0.59 0.60 1.00 1.85
Human (60kg) 0.081 0.135 0.162 0.189 0.216 0.324 0.316 0.324 0.54 1.00
Note
Table 2. Animal equivalent dose calculation based on BSA ratio.
A B Mouse
(20g)
Rat
(200g)
Guinea Pig
(400g)
Rabbit
(1.5kg)
Cat
(2.0kg)
Monkey
(4.0kg)
Dog
(12kg)
Human
(70kg)
Mouse (20g) 1.00 7.0 12.3 27.8 29.7 64.1 124.2 378.9
Rat (200g) 0.143 1.00 1.75 4.0 4.2 9.2 17.7 54.1
Guinea Pig (400g) 0.082 0.57 1.00 2.3 2.4 5.2 10.1 30.9
Rabbit (1.5kg) 0.036 0.252 0.441 1.00 1.07 2.3 4.5 13.6
Cat (2.0kg) 0.034 0.236 0.412 0.94 1.00 2.2 4.2 12.8
Monkey (4.0kg) 0.016 0.109 0.191 0.434 0.463 1.00 1.94 5.9
Dog (12kg) 0.008 0.056 0.099 0.224 0.239 0.52 1.00 3.1
Human (70kg) 0.0026 0.018 0.032 0.073 0.078 0.169 0.328 1.00
Note
Table 3. Administration volumes considered good practice (and possible maximal dose volumes)a
Species Route and volumes (ml kg−1)
Oral s.c. i.p. i.m. i.v. (bolus) i.v. (slow inj.)
Mouse 10 (50) 10 (40) 20 (80) 0.05b (0.1)b 5 (25)
Rat 10 (40) 5 (10) 10 (20) 0.1b (0.2)b 5 (20)
Rabbit 10 (15) 1 (2) 5 (20) 0.25 (0.5) 2 (10)
Dog 5 (15) 1 (2) 1 (20) 0.25 (0.5) 2.5 (5)
Macaque 5 (15) 2 (5) c (10) 0.25 (0.5) 2 c
Marmoset 10 (15) 2 (5) c (20) 0.25 (0.5) 2.5 (10)
Minipig 10 (15) 1 (2) 1 (20) 0.25 (0.5) 2.5 (5)
Note

a. For non-aqueous injectates, consideration must be given to time of absorption before re-dosing. No more than two intramuscular sites should be used per day. Subcutaneous sites should be limited to two or three sites per day. The subcutaneous site does not include Freund’s adjuvant administration.

b. Values in millilitres per site.

c. data not available.

d. Two sets of values are shown in each column: values on the left are intended as a guide to ‘good practice’ dose volumes for single or multiple dosing; values on the right, where given, are the possible maximal values. If maximal values are exceeded, animal welfare or scientific implications may result and reference to the responsible veterinary surgeon should be made. In some instances values are there to accommodate pharmacopoeial requirements.

e. Some of these suggested maximum values have been obtained from recent literature, but appear high when compared with ‘good practice’ values. The need for careful attention to animal welfare and the formulation of material used at high dose volumes are emphasized, particularly if repeat dosing is intended.

References