Is there a simple way to do this? How accurate is this estimation? And, what is the best publication about this topic?
Human equivalent dose (HED) mg/kg= Animal dose (mg/kg) × (Animal Km/ Human Km). Where Human Km= 37, Mouse Km= 3, Rat Km = 6
eg:- For mice 5 mg/kg
HED= 5 × (3/37) = 0.405 mg/kg
Km = Body weight (Kg)/ Body surface area (BSA) (m2)
Generally Human Km= 37 otherwise add body surface area (BSA) & body weight
REFERENCE: Sushil Middha- Kumann University
Check these references:
1) Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers.
2) Ensayos clínicos de primera administracio´n en humanos: Agencia Europea
del Medicamento (EMEA) frente a la FDA First-in-human clinical trials: Comparison of EMEA and FDA guidelines. Cándido Hernández-López.
Manekar's answer is good, it all boils down to body weights relationship. supposing one is using Rabbits,Hamsters, or G/pigs what is their Km?
There are formulae as others have pointed out, but they are really rough estimates that tend to err on the very cautious side (quite rightly). More logical is to work back from an effective concentration, if known. It could be at receptor tissue level in lab tests or animal plasma levels. Then you calculate the probably peak plasma level in a human volunteer assuming 100% absorption (at a rate that is like the animal Pk or a tmax at 30 mins is a reasonable estimate) and match it to that concentration. For first dose to man safety you then take a fraction of that which should depend on the inherent safety of the mode of action of the drug. Some biologics like antibodies are outside this logic although you can use say, 100th rather than a 10th for example because nobody could really criticise you. Then don't make the Tegenero mistake of dosing several volunteers at once.
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