Innovation Pharmaceuticals Inc (IPIX)

[BonelessCat]

Here is a paper with a title that is exactly what I've been saying, HED is only accurate in estimating the safe starting dose for an escalation trial. The paper discusses HED and use of the human animal conversion formula.

Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers
http://www.fda.gov/downloads/Drugs/Guidances/UCM078932.pdf

Yes, preclinical testing is used also for estimating the possible efficacious dose range. No one is disputing that. But, that estimate is not a direct mouse to human conversion using HED. It requires assessing differences among species in liver processing, bioavailability differences in delivery methods, and pharmacokinetic (clearance, volume of distribution) differences (3 species gives more information than two or just one).

From a 2009 paper: "Simple scaling of drug doses can be misleading for some drugs; correction for protein binding, physicochemical properties of the drug or species differences in physiological time can improve scaling. However, differences in drug transport and metabolism, and in the dose–response relationship, can override the effect of size alone." I've bolded the main points.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737649/