Assessment of Drug-Drug Interaction Potential

Project Background and Problem

The client planned to conduct two phase-3 studies to evaluate a small molecule drug being developed as adjunctive therapy. It was essential to evaluate potential drug-drug interactions (DDIs) between the investigational drug and other commonly used 40+ drugs in this patient population.

The sponsor conducted cytochrome P450 (CYP)-mediated and transporter-mediated drug-drug interaction (DDI) studies in vitro. Additional in vitro DDI studies were conducted for uridine diphosphate glucuronosyltransferase (UGT). The client came to XP Pharma to support an urgent need for speedy interpretation of the in vitro study results to determine the potential for clinical DDI with commonly used 40+ drugs in the patient population.

XP Pharma’s Support Services

We evaluated seven in vitro DDI studies and four human PK study reports. We identified CYP enzymes as potential perpetrators that affect the pharmacokinetics of the investigational drug. We also identified CYP enzymes that could be affected by the investigational drug. Further, we estimated the effect size based on physiologically based pharmacokinetic (PBPK) assessment based on area under the curve (AUC) ratios. We identified CYPs, UGTs, and transporters that are unlikely to cause potential DDIs with the investigational drug.