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.

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 (K_m) is used to estimate the human equivalent does (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.

Human equivalent dose calculation based on body surface area

Species	Reference body weight (kg)	Km factor	Km 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

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 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 (syntax error): {\displaystyle Dose2 = \frac{AED}{K_m\:ratio} * Weight_{human} = \frac{300 mg/kg}{12.3} * 80 kg = ~1951 mg}