Pharmacokinetics: metabolism and excretion

4 Pharmacokinetics


metabolism excretion





Questions



image How are drugs metabolized?

image How are drugs excreted?

image What factors alter drug 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.


image

Fig. 3.4.1 Drug metabolism. (A) Phase I and II reactions; (B) example of aspirin metabolism.



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).


The activity of drug-metabolizing enzymes can be altered under various situations that have implications for clinical efficacy.

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Jul 18, 2016 | Posted by in PHARMACY | Comments Off on Pharmacokinetics: metabolism and excretion

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