title: An Open-Label, Randomized Bioavailability Study of Alternative Methods of Oral Administration of Naloxegol in Healthy Subjects.
abstract: Naloxegol is a peripherally acting μ-opioid receptor antagonist approved as an orally administered tablet for the treatment of opioid-induced constipation. Patients with swallowing difficulties may benefit from alternative approaches to the oral administration of the whole-tablet formulation of naloxegol. This open-label, randomized, 4-period, 4-treatment, crossover, single-dose study (NCT02446171) evaluated the pharmacokinetic (PK) characteristics of crushed naloxegol 25-mg tablets (suspended in water) administered orally or by nasogastric tube and a naloxegol solution compared with the commercially available 25-mg tablet formulation in healthy volunteers. The PK profiles for the crushed tablet, whether administered orally or by nasogastric tube, and the 25-mg oral solution were similar to that of the 25-mg tablet administered orally. Compared with naloxegol commercial tablets, the relative bioavailability of naloxegol using 3 alternative methods of administration was approximately 100%. For each pairwise treatment comparison of the 3 alternative methods with the approved whole tablet, the geometric least-squares mean ratio ranges were 94.37%-100.04%, 94.83%-100.44%, and 97.05%-102.05% for area under the curve (AUC), AUC0-t, and maximum plasma concentration, respectively, and their 90% confidence intervals were entirely within the predefined 80% to 125% bioequivalence limits. Naloxegol was well tolerated when administered in both liquid and solid form.
authors.affiliation: AstraZeneca Pharmaceuticals LP, Waltham, MA, USA.
authors.forename: Khanh
authors.initials: K
authors.lastname: Bui
authors.affiliation: AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Birmingham
authors.affiliation: AstraZeneca Pharmaceuticals LP, Gaithersburg, MD, USA.
authors.forename: Ulysses
authors.initials: U
authors.lastname: Diva
authors.affiliation: AstraZeneca Pharmaceuticals LP, Gaithersburg, MD, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Berger
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007441:Intubation, Gastrointestinal; D008297:Male; D008875:Middle Aged; D009019:Morphinans / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D009019:Morphinans; D009292:Narcotic Antagonists; D011092:Polyethylene Glycols; C000589308:naloxegol
keywords: bioavailability; bioequivalence; naloxegol; oral formulation; pharmacokinetics