ABSTRACT
Xenobiotics eliminate from the body predominantly by renal excretion and hepatic metabolism. Both processes are discussed in more detail in Chapters 5 and 6. The major route of excretion of unchanged xenobiotics from the body is the kidney. The removal of unchanged compounds may also occur through other routes including biliary, pulmonary, salivary, mammary, and skin/dermal/ sweat glands. Liver, the major site of metabolism, is responsible for biotransformation of xenobiotics, in particular lipid-soluble compounds to pharmacologically active and/or inactive metabolites by the enzymatic reactions classied as Phase I and II metabolism (Chapter 6). Phase I metabolism is responsible for the formation of primary metabolites through oxidation, reduction, hydrolysis and hydroxylation, which may or may not be active pharmacologically, or reactive toxicologically. Phase II metabolism is responsible for the conjugation of unchanged and primary metabolites through acetylation, glucuronidation, sulfation, glutathione formation, etc. (see Chapter 6) leading to the formation of water-soluble conjugates. Although the major site of metabolism is the liver, other organs like the kidney, lung, skin, and gastrointestinal tract contribute signicantly to the overall metabolism of xenobiotics in the body. The ultimate outcome of metabolism is to modify xenobiotics to water-soluble and less toxic compounds and facilitate their removal from the body.
