Introduction to drug metabolism enzymes

Published on October 1, 2007 Reviewed on April 20, 2016   47 min

A selection of talks on Pharmaceutical Sciences

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This talk is an introduction to the enzymes of drug metabolism. It will be illustrated by using examples from pharmaceuticals. These examples are equally applicable to other xenobiotics.
A basic concept we need to understand with enzymes is the principle of hydrophobicity and lipophilicity. Hydrophobicity is the association of non-polar groups or molecules in an aqueous environment. It arises from the tendency of water to exclude non-polar molecules. Lipophilicity is the affinity a molecule for a lipophilic environment. We measure this in a biphasic system by determining the partition coefficient between an aqueous buffer and a lipophilic phase, such as octanol.
This schematic shows how lipophilicity is actually quantitated. The term we actually end up with is log D 7.4. The 7.4 defines the pH. D refers to distribution coefficient. And because the range is wide, we log the term, we will also see that this fits nicely with biological properties. The schematic shows that only the unionized drug can penetrate into the lipid phase. Drug which is present in the aqueous phase is a mixture of ionized and unionized drug. PKA determines proportion of unionized drug versus ionized drug. The actual intrinsic lipophilicity, or P, determines the partitioning of the unionized drug between the aqueous phase and the lipid.