Animal scale-up is discussed as a formal approach to drug distribution in the body which permits consideration of scale through the individual processes that occur. Some of these are physical, such as blood flows, tissue binding, and kidney clearances. Others are chemical, such as metabolic reactions. The physical processes often vary quite predictably among mammalian species, and much is known about these independent of any chemical reactions. Certain metabolic reactions vary greatly and unpredictably among species. The physical and chemical processes interact so that the relationship of the pharmacokinetics of any given drug between one species and another may be quite straightforward or it may be rather obscure unless the correct interaction is perceived. Methotrexate pharmacokinetics are reviewed in discussing the use of animal scale- up for a drug where only physical processes need be considered. Problems involving metabolism are illustrated for thiopental and cytosine arabinoside.
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