Open AccessPharmacokinetics, Safety, and CCR2/CCR5 Antagonist Activity of Cenicriviroc in Participants With Mild or Moderate Hepatic Impairment
Author(s) -
Lefebvre E,
Gottwald M,
Lasseter K,
Chang W,
Willett M,
Smith PF,
Somasunderam A,
Utay NS
Publication year - 2016
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12397
Subject(s) - cmax , pharmacokinetics , medicine , tolerability , gastroenterology , liver injury , antagonist , ccr5 receptor antagonist , pharmacology , nonalcoholic steatohepatitis , adverse effect , inflammation , receptor , fatty liver , nonalcoholic fatty liver disease , chemokine , chemokine receptor , disease
Cenicriviroc, a dual CCR2/CCR5 antagonist, is being evaluated for treatment of nonalcoholic steatohepatitis and liver fibrosis (CENTAUR; NCT02217475). As it is metabolized by the liver, cenicriviroc was investigated in hepatic‐impaired participants for pharmacokinetic changes. Participants with mild‐to‐moderate hepatic impairment (HI) (Child–Pugh class A ( N = 7) or B ( N = 8)) and matched controls ( N = 15) received cenicriviroc 150 mg once daily for 14 days. Serial blood samples were obtained on Days 1 and 14. Safety, tolerability, and effects on CCR2/CCR5 ligands, cytokines, and bacterial translocation biomarkers were evaluated. Cenicriviroc exposures were increased by moderate HI (AUC 0‐τ 55%, C max 29% higher) but were not with mild HI (AUC 0‐τ 38%, C max 40% lower). Cenicriviroc was well tolerated. Rapid and potent CCR2/CCR5 blockade was observed, not associated with increases in hepatic inflammation or bacterial translocation biomarkers. Study findings suggest that cenicriviroc 150 mg can be used in patients with mild‐to‐moderate HI.