• Khanh Bui, Fahua She, and Mark Sostek.
• AstraZeneca Pharmaceuticals, Wilmington, DE, USA.
• J Clin Pharmacol. 2014 Dec 1;54(12):1368-74.

AbstractNaloxegol is a peripherally acting µ-opioid receptor antagonist (PAMORA) in development for the treatment of opioid-induced constipation (OIC). The pharmacokinetics of a single oral 25-mg dose of naloxegol in plasma was assessed in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment and compared with healthy volunteers. Participants were matched for sex, age, and body mass index. Hepatically impaired patients exhibited a 17%-18% decrease in area under the plasma concentration versus time curve (AUC) despite similar maximum plasma concentrations (Cmax ). This was an unexpected finding given that naloxegol is primarily cleared by the hepatic route. Time to Cmax was shorter in patients with moderate impairment (0.6 hours) versus those with mild impairment (2.3 hours) or normal subjects (2.0 hours). Mean apparent terminal half-life (t½ ) was shorter in patients with mild (9.6 hours) and moderate (7.5 hours) hepatic impairment versus healthy subjects (11.3 hours). Reductions in enterohepatic recycling of naloxegol because of hepatic impairment may explain the observed decreases in AUC and t½ observed in these patients. Naloxegol was generally well tolerated, and mild or moderate hepatic impairment appeared to have minimal effect on its pharmacokinetics and safety.© 2014, The American College of Clinical Pharmacology.

24 keywords...

hide…