Abstract

Objectives: Fentanyl pectin nasal spray (FPNS) is formulated as a solution utilizing PecSys^®; pectin based enabling technology (Archimedes). On contact with the nasal mucosa the formulation will gel and modulate fentanyl absorption while limiting nasal drip or runoff. This single-dose volunteer study compared the pharmacokinetics of FPNS 100, 200, 400, and 800 µg doses and assessed bioavailability relative to oral transmucosal fentanyl (OTFC) 200 µg. Safety and dose proportionality were also examined. Subjects and methods: 16, opioid-naïve subjects were dosed on five separate visits under naltrexone block. FPNS doses were administered using a Pfeiffer device delivering 100 µl. Devices were filled with either 1.57 mg/ml (100 and 200 µg dosing) or 6.28 mg/ml fentanyl citrate (400 and 800 µg). Venous blood samples were collected up to 48 h after dosing and plasma fentanyl concentrations measured. Results: Median t_max values for FPNS ranged from 15 to 21 min post-dose and were dose-independent. At 200 µg C_max values were 2.3-fold higher for FPNS compared with OTFC. Mean relative bioavailability of FPNS to OTFC ranged from 103% to 163%. Dose proportionality for C_max and AUC_0–1 across the FPNS range was statistically confirmed. Drug absorption also increased in a close to dose-proportional manner for AUC_0–inf. Conclusions: FPNS has a shorter t_max, higher C_max and greater bioavailability than OTFC and is well tolerated. The dose proportionality of Cmax and AUC_0–1 was demonstrated. It is concluded that the pharmacokinetic profile of FPNS suggests this product is suitable for clinical investigation in breakthrough pain in cancer patients.

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 Centre
Nottingham Science and Technology Park
University Boulevard, Nottingham, NG7 2TN, UK
Email: [email protected]

Citation