The basic pattern of the metabolism of foreign compounds is the same in all species, in that most foreign compounds are metabolized in two phases, in the first of which the compound may be oxidized, reduced, or hydrolyzed and in the second the products of the first phase may undergo a synthesis or conjugation to form polar excretory products. Within this pattern, however, tremendous variations can occur, since the enzymes which catalyze the reactions of these phases can be influenced by a large number of factors, species being one of the most important of these factors. Species variations in the nature and extent of the biotransformation of foreign compounds are complex and sometimes unexpected. If any foreign compound (or xenobiotic) is administered to more than one species, although one can now predict the pathways of xenobiotic metabolism, it is almost certain that species differences in the amounts of the predicted metabolites formed and excreted will be found and in some cases gross differences in the actual routes of metabolism will be found.The metabolism of a xenobiotic is often related to its toxicity and its therapeutic activity, and since the testing of potentially useful chemicals for use in man is carried out in animals lower on the evolutionary scale than man, it is important to know whether tests on these animals can be extrapolated to man. Therefore a comparative study of metabolism in man and other species could be of value for suggesting a species likely to be useful for comparing the activity of a given compound with that in man. This is a big task, since thousands of chemical compounds are now used by man for various purposes and 1729 species of rodents, only a few of which are extensively used for testing (e.g., the rat) and 193 species of subhuman primates which are nearest to man on the accepted evolutionary scale. Apart from testing chemicals for safe use in man, there is also the problem of the toxicity of environment chemicals to wild life. Some species may be more sensitive than others to chemical pollutants, and this difference may well be related to species differences in metabolism and how the chemical is detoxicated and excreted by the animal.In studies, of comparative metabolism, there are obviously two main entities to be considered: the species and the compound; one can thus study the fate of one compound in many species or the fate of many compounds in one species.The study of one compound in many species has produced certain patterns and from this type of study there has emerged the suggestion that the animals nearest to man in the pathways of drug metabolism are the subhuman primates, particularly, the Old World monkeys (1, 2). Examples of compounds which have been studied in this way are phenylacetic acid (3), sulfadimethoxine (4), quinic acid (5), coumarin (6), 4-hydroxy-3,5-diiodobenzoate (7), and methanol (8). These studies show that Old World monkeys and sometimes New World monkeys are similar to man in both phase I and II reactions; the 7-hydroxylation of coumarin, th...
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