Drug-Drug Interactions

Potential drug-drug interactions are a major concern in patients undergoing polytherapy. Preclinical identification of potential inhibitors and inducers of drug metabolizing enzymes and transporters is  critically important in new drug development. In addition, since it is not possible to study every combination of potentially interacting drugs in the clinic, development of novel simulation and prediction methods for drug-drug and drug-disease interactions that allow extrapolation of clinical findings from one drug to another is critically important. We have several active research projects ongoing in the area of prediction, simulation and rationalization of complex drug-drug interactions. Such complex drug-drug  interactions include drug-drug interactions that involve inhibitory metabolites, drug-drug interactions that are a result of inhibition of multiple enzymes and/or transporters, drug-drug interactions that are complicated by genetic variability and interactions in which coexisting diseases such as renal or hepatic impairment affect the magnitude of the observed interaction. Our work is focused on improving our understanding of the clinical importance of metabolites in precipitating drug-drug interactions and in developing better methods for preclinical risk assessment of potential inhibitors or inducers of drug metabolizing enzymes and drug transporters. We are also actively working on developing new simulation and modeling methods for complex drug-drug interactions.

CRT-cover

Our work on multi-CYP inhibition highlighted in the cover of Chemical Research in Toxicology

Fluoxetine-inhibition

Our work on characterizing fluoxetine as an inhibitor of CYP2C19 and CYP3A4 highlighted in the cover of Drug Metabolism and Disposition

Omeprazole-inhibition

Our work on the role of omeprazole metabolites in clinical drug-drug interactions highlighted in the cover of Drug Metabolism and Disposition