A whole-body physiologically based pharmacokinetic (PBPK) model of elagolix was developed to quantitatively account for the contribution of metabolizing enzymes, transporters, and their interplay.

The PBPK model was able to adequately describe clinical pharmacokinetics data and recover the observed drug–drug interaction (DDI), demonstrating that the model is verified for the intended purpose.

Simulations using elagolix PBPK model informed labeling information regarding the DDI potential with digoxin (P-glycoprotein substrate) and midazolam (cytochrome P450 3A4 substrate) under dosing conditions that were not tested clinically.