Preclinical Drug Development: Drug Metabolism and in Vitro/in Vivo Predictions

The focus of this module is on the non-clinical phase of drug development and specifically on the methods used to predict a substance’s metabolism and pharmacokinetics in humans. We also discuss how this information contributes to rational drug development. You will be acquainted with the theoretical background but also get practical experience from using experimental systems that can be used to characterize substance biotransformation. We cover the in vitro - methods used in industry today to identify metabolizing enzyme, evaluate the risk of drug interactions or the formation of reactive metabolites, but also methods for quantitative determination and identification of unknown metabolites. Various computer-based prediction tools used in drug development are also introduced.

During a lab week you generate experimental data which you then process using different software. As a result, you also get training in computer-based modelling and simulation. Examples of exercises are: determination of plasma protein binding, determination of Vmax and Km from incubation experiments in liver microsomes, prediction of drug-drug interaction in human from an in vitro interaction study. For quantification of drugs / metabolites we use HPLC-UV. Lab reports are part of the examination, which gives you training in scientific writing.

Throughout the course, you will be part of a team of students working on an assignment called Candidate Drug (CD) selection. The aim is to select the most suitable CD for a specific indication, based on pre-clinical data on three alternative molecules.

You will employ state-of-the-art software such as SimCyp®, WinNonlin® and Molinspiration® for analysis and prediction. This applies to your own experimental results, as well as the data obtained in assignment. You will also get acquainted with simulation of a drug's pharmacokinetics using a physiologically-based pharmacokinetics model.

The module consists of lectures given by experts in the field, practical application of some of the experimental systems and analysis methods available, as well as data analysis and interpretation of the data obtained.

The course is examined by presentation of CD selection assignment and lab reports.

An important course for those who have an interest in drug discovery / development!