Pharmacometric Modeling of Naloxegol Efficacy and Safety: Impact on Dose and Label

N Al-Huniti; D Zhou; H Xu; S Aksenov; K H Bui; R Fox; G Helmlinger; D Stanski

doi:10.1002/cpt.719

Pharmacometric Modeling of Naloxegol Efficacy and Safety: Impact on Dose and Label

Clin Pharmacol Ther. 2017 Nov;102(5):741-744. doi: 10.1002/cpt.719. Epub 2017 May 26.

Authors

N Al-Huniti¹, D Zhou¹, H Xu¹, S Aksenov¹, K H Bui¹, R Fox¹, G Helmlinger¹, D Stanski¹

Affiliation

¹ Quantitative Clinical Pharmacology, AstraZeneca LP, Waltham, Massachusetts, USA.

PMID: 28548207
DOI: 10.1002/cpt.719

Abstract

Naloxegol is a peripherally acting μ-opioid receptor antagonist that was developed for the treatment of opioid-induced constipation. Modeling and simulation of naloxegol efficacy and tolerability informed selection of doses for phase III studies and provided comprehensive dosage recommendations for the naloxegol US package insert.

Publication types

Review

MeSH terms

Analgesics, Opioid / adverse effects
Animals
Constipation / chemically induced
Constipation / drug therapy
Constipation / metabolism
Dose-Response Relationship, Drug
Drug Labeling / legislation & jurisprudence
Drug Labeling / methods*
Drug Labeling / standards
Humans
Models, Biological*
Morphinans / pharmacokinetics*
Morphinans / standards
Morphinans / therapeutic use
Narcotic Antagonists / pharmacokinetics*
Narcotic Antagonists / standards
Narcotic Antagonists / therapeutic use
Polyethylene Glycols / pharmacokinetics*
Polyethylene Glycols / standards
Polyethylene Glycols / therapeutic use
Treatment Outcome

Substances

Analgesics, Opioid
Morphinans
Narcotic Antagonists
Polyethylene Glycols
naloxegol