Innovation Pharmaceuticals Inc (IPIX)

[KMBJN]

Re: equivalent doses between humans and mice, most like to use body surface area equivalence, instead of weight equivalence.

http://www.fasebj.org/content/22/3/659.full

200 mg/kg in mice * 3 = ~600 mg/m^2 dose per BSA (based on the average weight of a mouse of 20 g and body surface area of 0.007 m^2). So yes, on a strict BSA equivalence between mice and humans, 200 mg/kg is around 600 mg/m^2 (in both mice and humans).

From the article critiquing media understanding of converting mouse resveratrol doses to humans, they conclude:

"When animal studies such as those involving resveratrol are completed and media reports distort the dose translation between the study mice and the HED, misinformation regarding the effectiveness of resveratrol against a disease or condition hampers the significance of preclinical data. Understanding the more appropriate method based on BSA conversion for dose translation across species is an important issue for both the scientific community as well as the general public. Currently, BSA-based dose calculation is the most appropriate method and is far superior to the simple conversion based on body weight."

So, it's best to calculate species equivalent doses in mg/m^2 (based on body surface area) instead of mg/kg (weight equivalence), and important to compare apples to oranges.

Of course, this assumes the drug is metabolized similarly between species (similar pharmacokinetic profile) and has similar effects between species (similar pharmacodynamic profile), including the toxic effects (toxicokinetics).

There does appear to be a correlation between mouse LD10 and human MTD (http://www.ncbi.nlm.nih.gov/pubmed/8568013)

That all being said, I trust Menon's instincts on what he thinks are the relevant human doses of Kevetrin - around 100-200 kg/m^2 for efficacy without toxicity.

I would expect there to be a decent dose response curve, with higher doses of K giving better responses, so the higher we can go without dose limiting toxicities (while above the expected therapeutic range), the better.

Where did the # 200 mg/kg or ~600 mg/m^2 in mice come from again? Which cancer, which poster, etc...? Were the effective dose ranges consistent across different cancer types, different combinations of treatment, and different species?