Importance of the field: Predicting drug metabolism after oral administration is highly complex, yet indispensable. Hitherto, drug metabolism mainly focuses on hepatic processes. In the intestine, drug molecules encounter the metabolic activity of microorganisms prior to absorption through the gut wall. Drug biotransformation through the gastrointestinal microflora has the potential to evoke serious problems because the metabolites formed may cause unexpected and undesired side effects in patients. Hence, in the course of drug development, the question has to be addressed if microbially formed metabolites are physiologically active, pharmaceutically active or even toxic. In order to provide answers to these questions and to keep the number of laboratory tests needed low, predictive tools - in vivo as well as in silico - are invaluable.
Areas covered in this review: This review gives an outline of the current state of the art in the field of predicting the drug biotransformation through the gastrointestinal microflora on several levels of modelling.
What the reader will gain: A comprehensive review of the literature with a thorough discussion on assets and drawbacks of the different modelling approaches.
Take home message: The impact of the gastrointestinal drug biotransformation on patients' health will grow with increasing complexity of drug entities. Predicting metabolic fates of drugs by combining in vitro and in silico models provides invaluable information which will be suitable to particularly reduce in vivo studies.