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
Human Equivalent Dose Calculation based on Body Surface Area
Usually the correction factor (Km) is used to estimate the human equivalent does (HED) 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 animal dose in mg/kg to HED in mg/kg, either | |
|---|---|---|---|---|
| Divide animal dose by | Multiply animal dose by | |||
| Human | 60 | 37 | - | - |
| 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 |