The metabolization of drugs as a factor in the development of adverse drug reactions

When medicines cause side effects, we often assume that the original active substance is responsible for this. However, after ingestion, the active substance is processed (metabolized) by enzymes or attached to polar compounds in order to accelerate its excretion from the body. The original active substance undergoes chemical changes and drug metabolites are formed. These drug metabolites have their own characteristics and can also cause side effects. Recognizing, predicting and preventing these side effects requires knowledge of the metabolism of the parent drug, the formation of metabolites and their effects in the body. In this thesis we investigated the knowledge about the role of drug metabolization and metabolites on side effects. Various data sources have been explored and used for this purpose. Phenoconversion has also been investigated as a method to intervene in drug metabolization and prevent the formation of unwanted metabolites. It appears that the role of drug metabolism and the formation of drug metabolites in side effects is well recognized, but the available information is not yet fully exploited. For example, knowledge about certain chemical structures in medicines can be included more often in the recognition and prediction of known and unknown side effects. Once the role of drug metabolism and the formation of the drug metabolites in the development of the side effect is recognized, action can be taken to prevent side effects. Phenoconversion appears to be a suitable method to prevent the formation of unwanted metabolites and could be investigated and possibly be applied more often.