Dose Conversion Between Animals and Human by Allometric Scaling
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 simple empirical approach considers the sizes of individual species based on body surface area which is related to metabolic rate of an animal that is established through evolutionary adaptation of animals to their size. ^{[1]}
Key Points in Scaling of Dose
- Larger animals have lower metabolic rates
- Physiological process of larger animals is slower
- Larger animals required smaller drug dose on weight basis (mg/kg)
- Allometry accounts the difference in physiological time among species
- Do not apply allometric scaling to convert adult doses to kids
Correction Factor
Usually the correction factor (K_{m}) is used to estimate the human equivalent dose (HED) for different animal species. K_{m} 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 K_{m} factor for human is calculated by dividing 60 by 1.62, which is 37. As the K_{m} factor for each species is constant, the K_{m} ratio is used to simplify calculations.
Species | Reference body
weight (kg) |
K_{m} factor | K_{m} ratio |
---|---|---|---|
Human | 60 | 37 | - |
Mouse | 0.02 | 3 | 12.3 |
Hamster | 0.08 | 5 | 7.4 |
Rat | 0.15 | 6 | 6.2 |
Ferret | 0.3 | 7 | 5.3 |
Guinea Pig | 0.4 | 8 | 4.6 |
Rabbit | 1.8 | 12 | 3.1 |
Cat | 2 | 11.7 | 3.2 |
Monkey | 3 | 12 | 3.1 |
Dog | 10 | 20 | 1.9 |
Marmoset | 0.35 | 6 | 6.2 |
Squireel Monkey | 0.6 | 7 | 5.3 |
Baboon | 12 | 20 | 1.9 |
Micro pig | 12 | 27 | 1.4 |
Mini pig | 40 | 35 | 1.1 |
Human Equivalent Dose Calculation
The HED can be calculated by dividing the animal equivalent dose (AED) by the K_{m} ratio. The unit of HED and AED is mg/kg.
Failed to parse (syntax error): {\displaystyle HED = \frac{AED}{K_m\:ratio}}
To get the final dose in mg, HED must be multiplied by the human weight:
Failed to parse (syntax error): {\displaystyle Dose = HED * Weight_{human} = \frac{AED}{K_m\:ratio} * Weight_{human}}
For example, in ^{[2]} an NMN admission to mice with 100 mg/kg and 300 mg/kg per day was analyzed. That is equivalent to dose of a 80 kg human of
Failed to parse (syntax error): {\displaystyle Dose1 = \frac{AED}{K_m\:ratio} * Weight_{human} = \frac{100 mg/kg}{12.3} * 80 kg = ~650 mg}
Failed to parse (SVG (MathML can be enabled via browser plugin): Invalid response ("Math extension cannot connect to Restbase.") from server "https://wikimedia.org/api/rest_v1/":): {\displaystyle Dose2 = \frac{AED}{K_m\:ratio} * Weight_{human} = \frac{300 mg/kg}{12.3} * 80 kg = ~1951 mg}