Towards Individualized Drug Dosage : General Methods and Case Studies

Abstract: Progress in individualized drug treatment is of increasing importance, promising to avoid much human suffering and reducing medical treatment costs for society. The strategy is to maximize the therapeutic effects and minimize the negative side effects of a drug on individual or group basis. To reach the goal, interactions between the human body and different drugs must be further clarified, for instance by using mathematical models. Whether clinical studies or laboratory experiments are used as primary sources of information, greatly influences the possibilities of obtaining data. This must be considered both prior and during model development and different strategies must be used. The character of the data may also restrict the level of complexity for the models, thus limiting their usage as tools for individualized treatment.In this thesis work two case studies have been made, each with the aim to develop a model for a specific human-drug interaction. The first case study concerns treatment of inflammatory bowel disease with thiopurines, whereas the second is about treatment of ovarian cancer with paclitaxel. Although both case studies make use of similar amounts of experimental data, model development depends considerably on prior knowledge about the systems, the character of the data and the choice of modelling tools. All these factors are presented for each of the case studies along with current results. Further, a system for classifying different but related models is also proposed with the intention that an increased understanding will contribute to advancement in individualized drug dosage.