RLO: Clinical impact of changes in drug clearance

Genetic factors

Genetic polymorphisms or discrete variations in the sequence of certain genes can occur, and this is particularly true of the genes which code for the cytochrome P450 metabolising enzymes in the liver.

These enzymes can be either more or less active in some people, and this will impact on their ability to clear drugs through hepatic mechanisms. People with less active enzymes are poor metabolisers, while people with more active enzymes are rapid metabolisers. In rapid metabolisers, hepatic clearance will be increased, resulting in a shorter half-life of the drug. In poor metabolisers, hepatic clearance will be reduced, resulting in a longer half-life.

These genetic polymorphisms are often more prevalent in specific ethnic groups. For example, polymorphisms of the enzyme CYP2C19 affect up to 20% of the Japanese population, decreasing their ability to clear drugs such as lansoprazole, a proton pump inhibitor.

 

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