Species variations xenobiotic metabolism

Walker, C.H. (1980). Species variations in some hepatic microsomal enzymes that metabolise xenobiotics. Progress in Drug Metabolism 5, 118-164. 

In vitro Metabolism. Numerous variables simultaneously modulate the in vivo metabolism of xenobiotics therefore their relative importance cannot be studied easily. This problem is alleviated to some extent by in vitro studies of the underlying enzymatic mechanisms responsible for qualitative and quantitative species differences. Quantitative differences may be related directly to the absolute amount of active enzyme present and the affinity and specificity of the enzyme toward the substrate in question. Because many other factors alter enzymatic rates in vitro, caution must be exercised in interpreting data in terms of species variation. In particular, enzymes are often sensitive to the experimental conditions used in their preparation. Because this sensitivity varies from one enzyme to another, their relative effectiveness for a particular reaction can be sometimes miscalculated. 

Studies of antipyrine metabolism may be used to illustrate the effect of inhibition on metabolism in vivo in addition, these studies have demonstrated variation among species in the inhibition of the metabolism of xenobiotics. In the rat, a dose of piperonyl butoxide of at least 100 mg/kg was necessary to inhibit antipyrine metabolism, whereas in the mouse a single intraperitoneal (IP) or oral dose of 1 mg/kg produced a significant inhibition. In humans an oral dose of 0.71 mg/kg had no discernible effect on the metabolism of antipyrine. 

The metabolism of many drugs and foreign compounds is often species dependent. Different animal species may bio-transform a particular xenobiotic by similar or markedly different metabolic pathways. Even within the same species, individual variations (strain differences) may result in significant differences in a specific metabolic path way This... 

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