Year: 2025
Type: article
Study design: Clinical Trial
Abstract: Fruquintinib (FRUZAQLA TM ) is a highly selective tyrosine kinase inhibitor of all three vascular endothelial growth factor receptors (‐1, ‐2, and ‐3). Two Phase 1, open‐label, single‐dose studies investigated the impact of hepatic or renal impairment on the pharmacokinetics and tolerability of fruquintinib. Participants with moderate renal impairment (creatinine clearance [CrCl] 30‐59 mL/min; eight participants) and matched healthy controls (eight participants for each study) received fruquintinib 5 mg. Participants with moderate hepatic impairment (Child–Pugh B; eight participants) and severe renal impairment (CrCl 15‐29 mL/min; eight participants) received fruquintinib 2 mg. Pharmacokinetic samples were collected over 240 h. Fruquintinib pharmacokinetics were similar between participants with moderate hepatic impairment and healthy controls; geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for maximum plasma concentration (C max ), area under the plasma concentration–time curve from 0 to time of last measurable concentration (AUC 0‐t ), and AUC from 0 to infinity (AUC 0‐inf ) were 1.04 (0.87‐1.24), 0.89 (0.64‐1.23), and 0.91 (0.66‐1.26), respectively. Fruquintinib pharmacokinetics were similar between participants with severe or moderate renal impairment and healthy controls. Compared with healthy controls, the respective GMRs (90% CIs) for C max , AUC 0‐t , and AUC 0‐inf for participants with severe renal impairment were 0.89 (0.78‐1.03), 0.97 (0.83‐1.14), and 1.01 (0.85‐1.19), and for participants with moderate renal impairment were 0.95 (0.78‐1.15), 1.06 (0.89‐1.26), and 1.07 (0.89‐1.28). Fruquintinib was generally well tolerated. These results support fruquintinib use without dose adjustment (5 mg daily, 3 weeks on, and 1 week off) in patients with moderate hepatic impairment or moderate to severe renal impairment.
DOI: 10.1002/jcph.70040
Authors: Martha Gonzalez, Zhao Yang, William Schelman, Thomas C. Marbury, Juan C. Rondon, William Smith, Xiaofei Zhou, Neeraj Gupta, Caly Chien
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,150
OpenAlex ID: W4410260876