How does liver function impact the metabolism of a chemotherapy drug? This study examines the effect of moderate and severe hepatic impairment (HI) on the pharmacokinetics (PK) of trilaciclib, a cyclin-dependent kinase 4 and 6 inhibitor used to reduce chemotherapy-induced myelosuppression. Participants with moderate and severe HI, along with matched healthy controls, received a single intravenous dose of trilaciclib. The unbound fraction of trilaciclib was comparable across groups, but the unbound trilaciclib extent of exposure was higher in HI participants. Ad hoc analysis using National Cancer Institute classification showed similar results. The findings suggest that the standard trilaciclib dose should be reduced by approximately 30% for patients with moderate or severe HI to avoid potential toxicity. The US Food and Drug Administration‐approved trilaciclib dose of 240 mg/m2 should be reduced by ∼30%, to 170 mg/m2, for patients with moderate or severe HI.
Published in The Journal of Clinical Pharmacology, which focuses on the latest findings in drug development, clinical pharmacology, and therapeutics, this article directly aligns with the journal’s scope. By investigating the impact of hepatic impairment on drug pharmacokinetics, the study provides valuable information for optimizing drug dosing in specific patient populations and improving treatment safety.