Pharmacokinetics of Ribociclib in Subjects With Hepatic Impairment

Area of Science:

• Pharmacology
• Hepatology
• Oncology

Background:

• Ribociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6, approved for HR+, HER2- breast cancer.
• Hepatic metabolism via cytochrome P450 3A4 is the primary route for ribociclib elimination.
• Understanding ribociclib pharmacokinetics in hepatic impairment is crucial for safe and effective dosing.

Purpose of the Study:

• To characterize the pharmacokinetic profile of ribociclib in individuals with varying degrees of hepatic impairment.
• To determine if dose adjustments are necessary for patients with mild, moderate, or severe hepatic dysfunction.

Main Methods:

• A Phase 1, open-label, multicenter study administered a single 400 mg oral dose of ribociclib.
• Participants were stratified into four Child-Pugh classification cohorts: normal, mild, moderate, and severe hepatic impairment.
• Pharmacokinetic parameters were analyzed across the different hepatic function groups.

Main Results:

• Ribociclib exposure was comparable between subjects with normal and mild hepatic impairment.
• A moderate (approximately 30%) increase in ribociclib exposure was observed in subjects with moderate and severe hepatic impairment.
• The 400 mg dose was generally well-tolerated across all hepatic impairment levels.

Conclusions:

• No ribociclib dose adjustment is needed for patients with mild hepatic impairment.
• A reduced ribociclib dose of 400 mg daily (3 weeks on, 1 week off) is recommended for patients with moderate to severe hepatic impairment.
• These findings support individualized dosing strategies for ribociclib based on hepatic function.