View source for 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. <ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804402/</ref>

== 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<sub>m</sub>) is used to estimate the human equivalent dose (HED) for different animal species. K<sub>m</sub> 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<sub>m</sub> factor for human is calculated by dividing 60 by 1.62, which is 37. As the K<sub>m</sub> factor for each species is constant, the K<sub>m</sub> ratio is used to simplify calculations.
{| class="wikitable"
|+Human equivalent dose calculation based on body surface area
|-
!Species
!Reference body
weight (kg)
!K<sub>m</sub> factor
!K<sub>m</sub> 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<sub>m</sub> ratio. The unit of HED and AED is mg/kg.

<math>HED = \frac{AED}{K_m\:ratio}</math>

To get the final dose in mg, HED must be multiplied by the human weight:

<math>Dose = HED * Weight_{human} = \frac{AED}{K_m\:ratio} * Weight_{human}</math>

For example, in <ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668137/</ref> 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

<math>Dose1 = \frac{AED}{K_m\:ratio} * Weight_{human} = \frac{100 mg/kg}{12.3} * 80 kg = ~650 mg</math>

<math>Dose2 = \frac{AED}{K_m\:ratio} * Weight_{human} = \frac{300 mg/kg}{12.3} * 80 kg = ~1951 mg</math>

== References ==
<references />
[[Category:Research]]