Population pharmacokinetics of naloxegol in a population of 1247 healthy subjects and patients

British Journal of Clinical Pharmacology
Nidal Al-HunitiMark Sostek

Abstract

Naloxegol, a polyethylene glycol conjugated derivative of the opioid antagonist naloxone, is in clinical development for treatment of opioid-induced constipation (OIC). The aim of the study was to develop a population pharmacokinetic model describing the concentration vs. time profile of orally administered naloxegol, and determine the impact of pre-specified demographic and clinical factors and concomitant medication on population estimates of apparent clearance (CL/F) and apparent central compartment volume of distribution (Vc /F). Analysis included 12,844 naloxegol plasma concentrations obtained from 1247 healthy subjects, patients with non-OIC and patients with OIC in 14 phase 1, 2b and 3 clinical studies. Pharmacokinetic analysis used the non-linear mixed effects modelling program. Goodness of fit plots and posterior predictive checks were conducted to confirm concordance with observed data. The final model was a two compartment disposition model with dual absorptions, comprising one first order absorption (ka1 4.56 h(-1) ) and one more complex absorption with a transit compartment (ktr 2.78 h(-1) ). Mean (SE) parameter estimates for CL/F and Vc /F, the parameters assessed for covariate effects, were 115 (3.41) l h(-1) and...Continue Reading

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Jun 20, 2014·Journal of Clinical Pharmacology·Khanh BuiMark Sostek

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Citations

Sep 2, 2016·Therapeutic Advances in Gastroenterology·Wojciech Leppert, Jaroslaw Woron
May 16, 2017·Bioanalysis·Yan LiPaul Severin
May 27, 2017·Clinical Pharmacology and Therapeutics·N Al-HunitiD Stanski
Dec 19, 2015·Journal of Clinical Pharmacology·Khanh BuiNidal Al-Huniti
Jul 25, 2017·Journal of Drug Targeting·Anat Eldar-BoockRonit Satchi-Fainaro
Feb 23, 2019·Journal of Clinical Pharmacy and Therapeutics·Robert B RaffaJoseph V Pergolizzi
Mar 25, 2017·The Journal of Pharmacology and Experimental Therapeutics·Eike FloettmannMichael Eldon
Aug 27, 2019·Pharmaceutical Statistics·Mario NagaseNidal Al-Huniti
Apr 8, 2020·Antimicrobial Agents and Chemotherapy·Su-Hua ZhangBi-Kui Zhang
Dec 6, 2019·Peptides·Richard J Bodnar

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