IND-enabling DDI Studies

Patients are often treated with multiple simultaneous medications, which generates a risk for significant drug-drug interactions that may affect the efficacy of one or several drugs and even lead to hospitalizations. Hence, it is required that DDI risks are evaluated while developing new therapies.

The regulatory compliant DDI evaluation usually includes enzyme reaction phenotyping, CYP inhibition & induction and transporter inhibition & substrate assessment. The testing concentrations for the test article are chosen to represent clinically relevant or predicted concentrations. Testing concentrations may also be limited based on in vitro solubility or cytotoxicity. For evaluating these factors, several pre-tests can be included, such as free fraction in the in vitro incubation conditions or plasma, kinetic solubility, or cytotoxicity before proceeding to the actual study.