Pharmacokinetics, Safety, and CCR2/CCR5 Antagonist Activity of Cenicriviroc in Participants With Mild or Moderate Hepatic Impairment
| Autor: | M. Willett, Netanya S. Utay, K. Lasseter, P. F. Smith, W. Chang, M. Gottwald, Anoma Somasunderam, E. Lefebvre |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine CCR2 Time Factors Receptors CCR5 Receptors CCR2 Cmax CCR5 receptor antagonist Pharmacology Fatty Acid-Binding Proteins Permeability General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Humans Medicine General Pharmacology Toxicology and Pharmaceutics Demography business.industry Research Liver Diseases General Neuroscience Hepatic impairment Imidazoles General Medicine Middle Aged Blockade Intestines 030104 developmental biology chemistry Tolerability Phase Forward Bacterial Translocation Case-Control Studies Sulfoxides Cytokines Female 030211 gastroenterology & hepatology Inflammation Mediators business Biomarkers Flagellin Cenicriviroc |
| Zdroj: | Clinical and Translational Science |
| ISSN: | 1752-8062 1752-8054 |
| DOI: | 10.1111/cts.12397 |
| Popis: | 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 (AUC0-τ 55%, Cmax 29% higher) but were not with mild HI (AUC0-τ 38%, Cmax 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. |
| Databáze: | OpenAIRE |
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