Abstract

Objectives: To optimize the absorption profile and reduce C_max, three new fentanyl nasal spray formulations have been developed: fentanyl pectin (FPNS), fentanyl chitosan (FChNS) and fentanyl in chitosan-poloxamer 188 (FChPNS). The venous pharmacokinetic profiles and tolerability of these formulations were assessed and compared with oral transmucosal fentanyl citrate (OTFC) lozenge. Subjects and methods: This randomized, open-label, crossover study was conducted in opioid-naïve, healthy adult volunteers. Subjects were dosed under naltrexone blockade on four occasions with three nasal sprays (100 µg in 100 µl) and OTFC 200 µg. Fentanyl venous plasma concentrations were measured up to 24 h post-dose. Tolerability was assessed by clinical nasal assessments and a nasal reactogenicity questionnaire. Results: 18 subjects were enrolled and completed the study. The mean dose-normalized AUC_0-∞ for each nasal formulation was significantly higher (p < 0.05) compared with OTFC. Bioavailability compared with OTFC was significantly greater for all nasal fentanyl formulations (FPNS 132.4%, FChNS 154.1%, FChPNS 122.3%). Median t_max (FPNS 0.33 h, FChNS 0.17 h, FChPNS 0.26 h) were significantly (p < 0.001) reduced (OTFC 1.5 h) and mean C_max significantly increased with all nasal formulations compared with OTFC. Nasal reactogenicity symptom incidence was lowest for the FPNS formulation (FPNS 2, FChNS 28 and FChPNS 45). Conclusions: All nasal formulations demonstrated significantly increased systemic exposure and reduced times to peak plasma values compared with OTFC. The FPNS formulation exhibited the most favorable nasal and general tolerability profiles. It appears suitable for further investigation in breakthrough cancer pain management.

Author Details

Authors

• A. Fisher¹
• M. Watling¹
• A. Smith¹
• A. Knight²

Departments

• ¹ Archimedes Development Limited, Albert Einstein Centre, Nottingham Science and Technology Park, University Boulevard, Nottingham, and
• ² Evicom Limited, Somerset House, Teddington, UK

Address

A. Fisher, PhD
Archimedes Development Limited
Albert Einstein Center
Nottingham Science and Technology Park
University Boulevard
Nottingham, NG7 2TN, UK
Email: [email protected]

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