Translating animal studies

[NHE]

Many of us have read journal papers on some compound used in an animal study that may have been effective for some purpose. However, the dosages used are often quite high especially when converted on a straight mg/kg basis. For example, one study I recently read used 400 mg/kg/day of a compound in mice. Using a straight mg/kg conversion, this suggests that the equivalent human dose should be around 27.2 g/day for a 150 lb person. For the average supplement, this could make use of the supplement "at the same level" prohibitively expensive. However, the above calculation may be in error and it may be more appropriate to convert the dosages based on an equation using a ratio of body surface areas. This is precisely the point made in the paper listed below. User their model, the above 400 mg/kg/day mouse dose converts to a more reasonable 32 mg/kg/day or 2.21 g/day for a 150 lb person.



Dose translation from animal to human studies revisited.
FASEB J. 2008 Mar;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. Free full text.