Wednesday, 13 November 2013

Dosing Animals to Man

Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008;22(3):659-61.

As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allometric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves the health and life span of mice. Immediately after the online publication of these papers, the scientific community and popular press voiced concerns regarding the relevance of the dose of resveratrol used by the authors. The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight, as was reported. For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.


Although I have known about a web resource (ref 7)  about translating doses of drugs from animals to man, I missed this one.

This may be an interesting read. Think about this when ever you read an animal study, because you need to think...."Is this dose relevant to human use?". 

This study indicates that you need to give a mouse about 12 times more drug to get a similar effect in humans. This is because rodents break down drugs much quicker than humans

In drug studies you can keep going up and up and up with the dose until it does something. In EAE this can be stressing the animals to such an extent that they do not get disease. 

I am sure many of the treatments published occur because of this. i.e. the drugs work because they stress the animals because of side effects

A few weeks ago we heard about a new drug that caused remyelination when used at 10mg/kg in a mouse the human dose is 0.01mg/kg using this  formula how would this compute?

4 comments:

  1. Do you guys ever read over what you've written? How are you working as professors?

    ReplyDelete
  2. Perhaps not straight away... so yes there are mistakes.

    Sometimes you have to make allowances for people with linguistic disabilities or people that can't type on smart phones.

    They may get re read amended during the day or night.

    If we had a copy editor who had the time to check the content, but we don't we are human and make mistakes soory

    ReplyDelete
  3. I finally made it to pubpeer to post everything.

    Here it is: https://pubpeer.com/publications/6F9ADD54F2E6004F2BDA9D0CC6195C#fb7190

    ReplyDelete

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