Extrapolation of pharmacological and toxicological data based on metabolic weight

Small animal species require higher doses of drugs and more frequent administrations than larger species. However, when drugs are metabolized to a toxic by-product, the contrary may be true. For many non-carcinogenic products a valid relationship has been found to exist between dose, plasma levels, body size, and response. Extrapolation of pharmacological and toxicological data based on metabolic weight (W body 0.756) seems to be safe within the groups of ruminants and monogastric herbivores as well as from one carnivorous species to another. If great variations are observed in response of some animal species, with no relationship to animal size, it will be unlikely that any prediction can be made for other animal species. If pharmacokinetic equivalence is critical, pharmacokinetic studies should be conducted to ensure that dosage regimens are equivalent in each species. The dosing guidelines suggested on the basis of metabolic weight apply to testing of drugs, consumer products, and environmental contaminants. The approaches suggested in the discussion for a solution to the problem may help expanding possibilities for extrapolation of pharmacological and toxicological data from laboratory animal to those relevant to man and other mammalian species.