Pharmacokinetics, Safety, and CCR2/CCR5 Antagonist Activityof Cenicriviroc in Participants With Mild or Moderate Hepatic Impairment

被引：46

作者：

Lefebvre, E. ^{[1
]}

Gottwald, M. ^{[1
]}

Lasseter, K. ^{[2
]}

Chang, W. ^{[1
]}

Willett, M. ^{[3
]}

Smith, P. F. ^{[4
]}

Somasunderam, A. ^{[5
]}

Utay, N. S. ^{[5
]}

机构：

[1] Tobira Therapeut Inc, San Francisco, CA 94080 USA

[2] Clin Pharmacol Miami Inc, Miami, FL USA

[3] Ready Clin LLC, Princeton, NJ USA

[4] D3 Med LLC, Parsippany, NJ USA

[5] Univ Texas Med Branch, Galveston, TX 77555 USA

来源：

CTS-CLINICAL AND TRANSLATIONAL SCIENCE | 2016年 / 9卷 / 03期

关键词：

FATTY LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; HEPATOCELLULAR-CARCINOMA; FIBROSIS; INJURY; MACROPHAGES; ADULTS; CCR2; TRANSPLANTATION; ASSOCIATION;

D O I：

10.1111/cts.12397

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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-)55%, C-max 29% higher) but were not with mild HI (AUC(0-) 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.

引用

页码：139 / 148

页数：10

共 38 条

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