Measurement of urinary metabolites of xenobiotics as a non-invasive technique in toxicology

Abstract

Most xenobiotics undergo biotransformation in living organisms and are excreted as metabolites in urine. There are three major reasons why the measurement of urinary metabolites may be important in toxicology: To obtain pertinent information on the biotransformation of a compound in the body. By identifying metabolites it is often possible to assess which metabolic pathways at the enzymic level are followed and whether, for example, reactive intermediates are formed. Also quantitative and kinetic information on the disposition of a xenobiotic can be obtained. To use in exposure tests (biological monitoring). The metabolites may be specific or nonspecific for the compound to which exposure takes place. To use as a measure for the activity of metabolic pathways in order to assess interindividual differences in biotransformation, or to assess changes in such pathways by exposure to or ingestion of xenobiotics. In particular in the identification of genetically determined polymorphism of metabolism in man, urinary metabolites have proved to be a very useful tool. Large interindividual differences in the rate of biotransformation of xenobiotics exist and this has important biological (toxicological) implications. The possible value of measuring the urinary metabolite profile of the model compound antipyrine, as a tool in the assessment of the activity of different xenobiotic oxidizing enzymes, is discussed.