Pharmacokinetics and relative bioavailability of fentanyl pectin nasal spray 100 - 800 µg in healthy volunteers.

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 trans-mucosal fentanyl (OTFC) 200 μg. Safety and dose proportionality were also examined. Subjects and methods: 16, opioid-naive 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-∞ . Conclusions: FPNS has a shorter t max , higher C max and greater bioavailability than OTFC and is well tolerated. The dose proportionality of C max 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.