Replies to post #79514 on Innovation Pharmaceuticals Inc (IPIX)

[NanoEngineer]

Do you claim that Dr Menon is wrong and that you are right ?

You have already been told that Dr Menon mentioned that the efficacy range for Kevetrin on human is estimated to be around 200mg/m2. We are currently well above that level.

Do you claim that Dr Menon does not know how to estimate the K dosing level required to reach efficacy ?

BigK and you are both wrong!!!

Preclinical doses are used to estimate the effective human dose.

Unfortunately, to get the same or similar results in humans as has been touted in preclinical animal studies will require much much higher doses than the current dose for the ninth cohort.

You all better hope and pray that the MTD for Kevetrin isn't reached for at least a few more cohorts.

[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/