DDI and Drug Development

Drug-drug interactions (DDIs) comes as a result of action two or more drugs taken simultaneously by the same patient. They can be clinically relevant or no. Treatment failure or drug toxicity can be a consequence of significant DDIs. Assessment of DDIs is one of the most important steps in a process of the development of a new molecular entity as well as the future risk-benefit evaluation. The main regulatory bodies like European Medical Agency (EMA), US Food and Drug Administration (FDA), and Japanese Pharmaceuticals and Medical Device Agency (PDMA) made guidelines with detailed recommendations to recognize DDIs using different type tests (in silico, in vitro, preclinical and clinical) to assess DDI risk and informed the patient about proper management. The advanced in vitro methodology and modeling significantly improved our knowledge and understanding of DDI mechanisms and tools for recognizing and predicting them. The evaluation of DDI risk includes a clinical DDI study, as a central part of the process. Moreover, clinical DDI studies are a powerful tool for detecting DDIs and help us to explain their mechanisms, which can be confirmed by in vitro methods through the process of reverse translation. DDI clinical assessment cannot cover each permutation of different parameters involved in the outcome. In silico models together with mechanistically focused clinical development are the basis for understanding the clinical relevance of DDIs. There is no standard and optimal schedule to examine DDIs, but the design of each study has to be grounded carefully, based on the availability of in vitro and clinical data, to ensure the usefulness of the study and protect the subject’s safety. This chapter tries to follow an assessment of DDI through the drug development process.