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An Open‐Label, Randomized Bioavailability Study of Alternative Methods of Oral Administration of Naloxegol in Healthy Subjects
Author(s) -
Bui Khanh,
Birmingham Bruce,
Diva Ulysses,
Berger Bruce
Publication year - 2017
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.335
Subject(s) - medicine , bioavailability , randomized controlled trial , traditional medicine , pharmacology
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), AUC 0–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.