With the increasing use of wastewater for irrigation of farmland, and thus the potential uptake and translocation of pharmaceuticals and their metabolites in crops, concerns about food safety are growing. After their uptake, plants are able to metabolize drugs to phase I, phase II, and phase III metabolites. Phase I reactions closely resemble those encountered in human drug metabolism, including oxidations, reductions, and hydrolysis. Phase II reactions, in turn, encompass conjugations with glutathione, carbohydrates, malonic acid, and amino acids. In phase III, these conjugates are transported and stored in the vacuole or bound to the cell wall. Pharmaceutical metabolism in plants has been investigated by using different approaches, namely, the use of whole plants grown in soil or hydroponic cultures, the use of plant tissues, and the incubation of specific plant cell suspensions. While studies relying on whole plants require long growth periods and more complex analytical procedures to isolate and detect metabolites, they constitute more realistic scenarios with the ability to determine site-specific metabolism and the translocation within the plant. The advantage of in vitro studies lies in their rapid setup. Recent advances in plant-microbiota investigations have shown that the plant microbiome modulates the response of the plant towards pharmaceuticals. Rhizospheric and endophytic bacteria can directly contribute to pharmaceutical metabolism and influence plant uptake and translocation of pharmaceuticals and their metabolites. Additionally, they can have beneficial properties for the host, contributing to plant health and fitness. This chapter gives an overview of human and plant drug metabolism followed by a comparison of different models used to identify pharmaceutical metabolites and their metabolic pathways in plants. A description of the mechanisms and reactions originating these metabolites is concisely presented. Finally, the role of the microbiome is critically discussed with examples of synergies between plants and their associated microbiota for pharmaceutical degradation.
