Thus, our research focuses on identifying factors that contribute to variable drug disposition. Completed and ongoing bench and clinical studies in our laboratory address the impact of altered drug metabolizing enzymes and drug transporters due to genetic polymorphisms and nongenetic factors (e.g., DDIs) on exposure of drugs and (active) metabolites. Our research activities include: developing new analytical tools to measure drugs and their metabolites; profiling of drug metabolites; identification of rate limiting metabolic pathways and the specific enzymes involved; developing and validating novel molecular and clinical tools to study drug disposition and DDIs; assessing the impact of genetic variants and DDIs as well as interplay of them on drug exposure and effect; and developing mathematical models (e.g. static models, PBPK and popPK) to allow mechanistic understanding and quantitative prediction of clinical drug exposure and DDIs from in vitro data.
