4 Pharmacokinetics
metabolism excretion
Drug metabolism
The liver is the major organ for the biotransformation of drugs. Hepatic cytochrome P450 (CYP) actively metabolizes endogenous and exogenous chemicals to metabolites that are, in general, more polar; this promotes elimination from the body and terminates drug action. In some cases, the metabolite may itself have potent biological activity or have toxic properties. Essentially, two types of biotransformation can occur.
Phase 1
CYP belongs to a family of haem-containing enzymes and is the major catalyst of drug biotransformation involving oxidative and reductive reactions. It has evolved to biotransform a wide variety of environmental chemicals, food toxins and drugs (Fig. 3.4.1). Oxidation requires NADPH.
Phase 2
These reactions involve the formation of a covalent link between an exposed functional group on a parent compound with glucuronic acid, sulphate, glutathione, amino acids or acetate. This conjugation process results in a highly polar water-soluble metabolite, which is generally inactive and rapidly excreted into the urine or faeces (Fig. 3.4.1).
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