Absorption: Interspecies Differences
Interspecies differences in the gastrointestinal absorption of xenobiotics have generally been regarded of minor significance in explaining differential susceptibilities to such agents. This has been stated rather forcibly by Rail (1969), who has correctly emphasized the role of differential metabolism of xenobiotics as the principal explanation for interspecies variations. The biological–chemical basis for such a conclusion is derived from a long list of examples where striking differences in species sensitivity are best explained by different abilities to either biointoxify or detoxify certain compounds. Along with the widely accepted occurrence of differential interspecies metabolic capabilities was the general recognition that the passage of a compound across the lipoid membrane differed only slightly across species and could substantially be explained according to the physicochemical properties of the molecule, membrane, and local environment. Numerous tests have been devoted to describing and analyzing the mechanisms of gastrointestinal tract absorption, passive diffusion, facilitated diffusion, active transport, filtration through membrane pores, phagocytosis, and pinocytosis, 10among others. The vast majority of xenobiotics tend to transverse lipoid membranes via passive diffusion, with the rate of diffusion contingent on the lipid solubility of the substance and its degree of ionization.