Metabolism involves a set of chemical reactions that modifies a molecule into another e.g. for storage or further chemical reactions.
The metabolism of a chemical and its subsequent transport determines its clearance, clinical efficacy and, ultimately, its toxicity. The main site of metabolism is the liver but other organs, such as the intestine and skin are also sites of metabolism, especially for orally or topically applied ingredients, respectively.
Different organs express different metabolising enzymes and exhibit different capacities to metabolize compounds. It is therefore essential to understand how each organ contributes (if at all) to the fate of a chemical once it enters the skin and/or systemic circulation.
There are numerous chemicals that come into contact with the skin, such as those in cosmetics, as well as pollutants and pesticides. Information on the metabolism of a chemical as it passes through the skin is needed to make a hazard/safety assessment. Intact skin from multiple sites, cells, cytosol, homogenate, microsomes, S9 can all be used to investigate the dermal metabolism of a test compound.
The oral bioavailability of many drugs is limited by metabolism in the intestine, which can be investigated using isolated cells and sub-cellular fractions (cytosol, homogenate, microsomes, S9).
HepaRG™ cells, primary hepatocytes (incubated in serum-free or plasma containing medium), or liver sub-cellular fractions (cytosol, homogenate, microsomes and S9 with appropriate co-factors) can all be used to investigate the hepatic metabolism of a test compound.
The use of human plasma in hepatocyte incubations has been shown to improve the prediction of in-vivo hepatic clearance.
The kidney has also been shown to have a large capacity to metabolize many drugs, hormones, and xenobiotics. Therefore, the potential of a drug to be metabolised by the kidney should be considered, especially since the metabolites could cause toxicity.