Physiologically-Based Pharmacokinetics of Ribociclib Drug-Drug Interactions and Organ Impairment Pharmacokinetics in Early Breast Cancer. (PubMed, Pharmaceuticals (Basel))
PBPK modeling predicted that ritonavir or erythromycin (strong and moderate CYP3A4 inhibitors) would increase ribociclib steady-state area under the concentration-time curve (AUC) by 1.84-fold or show no meaningful impact, respectively. Steady-state ribociclib AUC was estimated to decrease by 83% and 74% with rifampicin and efavirenz, strong and moderate CYP3A4 inducers, respectively. Ribociclib was estimated to increase CYP3A4 substrate midazolam exposure by 280%. Mild HI or mild/moderate RI did not show an apparent impact on ribociclib PK. Using relevant data and methodology for EBC patients, this analysis informed the approved ribociclib label of no dose adjustment for EBC patients with concomitant use of a moderate CYP3A inhibitor, any degree of HI, or mild/moderate RI, and a reduced 200 mg dose for patients with concomitant use of a strong CYP3A inhibitor or severe RI.
