Xenobiotic disposition metabolism

R Kato, RW Eastbrook, MN Cayen. Xenobiotic Metabolism and Disposition. London Taylor Francis, 1989, p 109. 

Miyamoto, J. 1988. Disposition and metabolism studies of xenobiotics in the environment fundamentals for safety assessment. Jour. Toxicol. Sci. 13 221-246. 

If toxicology can be described as the study of the effects of a chemical on an organism, metabolism can be described as the opposite the effects of the organism on the chemical. Metabolism refers to a process by which a drug (xenobiotic) is chemically modified by an organism. It is part of the overall process of disposition of... 

More than 130 years ago, Keller (1 ) reported the isolation of hippuric acid (benzoylglycine) from the urine of horses fed pure benzoic acid and so ushered in our modern era of metabolism investigations on xenobiotics (foreign substances in the environment). In addition to the valuable basic knowledge of the biological processes of terrestrial animals provided by such studies, the advent of regulations controlling the use of pesticides stimulated research on the disposition of these chemicals by both mammals and insects (2). 

Standardized techniques and equipment for such investigations are in widespread use. Unfortunately, the same cannot be said for metabolism investigations in aquatic animals. Most of the world s animals exclusive of the insects —over 200,000 known species -- live at least a part of their lives in water over 100 species have major economic importance and they form the populations most often at risk of exposure to a growing number of chemical pollutants, but science remains largely ignorant of the disposition of xenobiotics by intact, living specimens of even the most common of the aquatic animals. 

Caldwell, J. (1992) Problems and opportunities in toxicity testing arising from species differences in xenobiotic metabolism. Toxicol. Lett., 64/65, 651-659 Caldwell, J., Anthony, A., Cotgreave, I.A. Sangster, S.A., Sutton, J.D., Bernard, B.K. Ford, R.A. (1985) Influence of dose and sex on the disposition and hepatic effects of cinnamyl anthranilate in the B6C3F1 mouse. Food chem. Toxicol., 23, 559-566 Cattley, R.C., DeLuca, J., Elcombe, C., Fenner-Crisp, R, Lake, B.G, Marsman, D.S., Pastoor,... 

There are many factors, both chemical and biological, which affect the disposition of xenobiotics. Chemical factors include size and structure, pKa, chirality, and lipophilicity. Biological factors include species, sex and strain, genetic factors, hormonal influences, disease and pathological conditions, age, stress, diet, dose, enzyme induction and inhibition, and tissue and organ specificity. All of these factors can affect the toxicity of a chemical by changing its disposition, especially its metabolism. 

Illing, H.P.A., Ed., Xenobiotic Metabolism and Disposition, CRC Press, Boca Raton, FL, 1989. 

Our first indication that fermentable fiber could alter microfloral metabolism was based on studies assessing the influence of dietary fiber types on the disposition of model xenobiotics using pharmacokinetic analysis (14). Amaranth was selected as a model xenobiotic for these studies because it was absorbed only after reduction by gut microflora (15). 

A. DAVID RODRIGUES is Executive Director, Metabolism and Pharmacokinetics, Bristol-Myers Squibb, Pharmaceutical Research Institute, Princeton, NJ, and received his Ph.D. in Biochemistry from the University of Surrey, Guildford, UK. Dr. Rodrigues is a member of the American Association of Pharmaceutical Scientists and is presently serving on the Scientific Affairs Committee of the International Society for the Study of Xenobiotics. He has authored more than 75 peer-reviewed articles and over one dozen book chapters, and sits on the Editorial Board of three journals (Drug Metabolism and Disposition, Drug Metabolism Letters, and Current Drug Metabolism). 

Factors affecting metabolism and disposition of drugs or xenobiotics in vivo have been amply described elsewhere (Timbrell, 1991). They may be divided into biological factors and molecular factors. 

Green, M.D., King, C.D., Mojarrabi, B., Mackenzie, P.I. and Tephly, T.R. (1998) Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP-glucuronosyltransferase 1A3. Drug Metabolism and Disposition The Biological Fate of Chemicals, 26, 507-512. 

Fig. 3 Incorporation of xenobiotic metabolism into kinetic, dispositional, and regulatory processes in the cell and its environment...

---