An evaluation of the drug interaction potential of netupitant with substrates, inhibitor and inducer of CYP3A4.

e19533 Background: Neurokinin-1 receptor antagonist (NK1 RA) is commonly administered in combination with a 5-HT3 RA such as palonosetron (PALO) to prevent the stimulus of nausea and vomiting caused by emetogenic chemotherapy. Netupitant (NETU), a new NK1 RA under evaluation for its antiemetic efficacy and tolerability, is both a substrate for and a competitive inhibitor of CYP3A4. Two studies were designed to determine the potential risk for drug-drug interaction in clinical practice. In the first study, the effects of NETU on the metabolism of two representative CYP3A4 substrates, erythromycin (ERY) and midazolam (MID) were determined. In the second study, a CYP3A4 inhibitor, ketoconazole (KETO), or an inducer, rifampicin (RIF) was coadministered with a fixed dose combination of NETU/PALO to observe the potential effects on NETU and PALO metabolism. Methods: Serial blood samples were collected from healthy volunteers and pharmacokinetic (PK) parameters were determined in both studies. The first trial wa...