In Vitro Models for Metabolism: Applicability for Research on Food Bioactives

In vitro models are the natural continuation of in silico predictions being carried out and form the missing link between in silico and in vivo. In vitro metabolism models aid in the fast and systematic selection of new lead compounds and designing of human and/or animal studies, offer explanations of possible mechanisms of action, etc. Metabolism studies also provide insights on safety and toxicity aspects. Access to metabolism information, as key determinant of bioavailability, generated via in vitro and in silico methods will save time and costs in the selection of lead compounds, planning of intervention studies, design of products and determining potential mechanisms of action. This chapter highlights the importance of metabolism on bioavailability and determining the success or failure (efficacy and toxicity) of a product.Metabolism occurs mainly in the liver and intestine and is a major factor affecting the systemic bioavailability of food actives and the concentrations available to exert potential activity at the targeted sites of action. Hence, metabolism is a large determinant of the functional value attributed to a compound. This chapter should help in the selection of the most applicable in vitro biotransformation model to answer questions around metabolism and bioavailability. Metabolism in the liver and intestine is described in detail and the possible in vitro models are presented with their ad- and disadvantages. A conclusion is reached as to what the most applicable system may be and which criteria should be considered when selecting an appropriate system.Key information provided: • intestine and liver are both significant sites of metabolism •in vitro models vary from simple to complex (reflecting characteristics such as the robustness of the system, data obtained and costs) the complexity of a model will be based on the question(s) that need to be answered (e.g. target and compound specific) • most commonly used in vitro models available are either sub-cellular (microsomes, S9 fractions or SupersomesTM) or cellular (hepatocytes, enterocytes) • human microsomes (hepatic and intestinal) and hepatocytes are the 2 recommended systems for first experiments •“pooled” mix-gender microsomes and hepatocytes generate a broader overview of the human population (e.g. decrease complications due to large inter-individual differences)In vitro models attempt to predict in vivo events with some models stronger and more conclusive than others, but no model is complete. Generally, the more robust models are also more costly (e.g. hepatocytes vs. microsomes). One must weigh the pros and cons and select the model which best suits the questions at hand and is still reasonably cost-effective. Follow-up in vivo studies (animals or humans) to confirm in vitro predictions are almost always required.