Absorption, distribution, and excretion in complex organisms

Abstract If the dose makes the poison, then the concentration of a toxicant at its site of action will dictate the magnitude and duration of adverse effects. For a xenobiotic to reach the systemic circulation, it must move through or between the epithelial cells at the site of entry. Both passive diffusion and active transport facilitate absorption. The physicochemical properties of the xenobiotic govern its distribution, in combination with the anatomical and physiological characteristics of the organism. As sufficient concentrations of the xenobiotic reach the target site, adverse effects ensue. Numerous body systems exist to detoxify and eliminate the offending toxicant, such as renal, biliary, and respiratory excretion and metabolism. As the toxicant is cleared from the body, xenobiotic concentrations in tissues fall, terminating reversible toxic effects. Taken together, absorption, distribution, metabolism, and excretion encompass the ADME processes and contribute to the extent and length of toxicity.