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

Author(s): Fisher A, Watling M, Smith A, Knight A

Affiliation(s): Archimedes Development Limited, Albert Einstein Centre, Nottingham Science and Technology Park, University Boulevard, Nottingham, UK. tonyfisher@archimedespharma.com

Publication date & source: 2010-12, Int J Clin Pharmacol Ther., 48(12):860-7.

Publication type: Clinical Trial, Phase I; Randomized Controlled Trial

OBJECTIVES: Fentanyl pectin nasal spray (FPNS) is formulated as a solution utilizing PecSys(R); 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 microg doses and assessed bioavailability relative to oral transmucosal fentanyl (OTFC) 200 microg. 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 microl. Devices were filled with either 1.57 mg/ml (100 and 200 microg dosing) or 6.28 mg/ml fentanyl citrate (400 and 800 microg). Venous blood samples were collected up to 48 h after dosing and plasma fentanyl concentrations measured. RESULTS: Median tmax values for FPNS ranged from 15 to 21 min post-dose and were dose-independent. At 200 microg Cmax 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 Cmax and AUC0-1 across the FPNS range was statistically confirmed. Drug absorption also increased in a close to dose-proportional manner for AUC0-inf. CONCLUSIONS: FPNS has a shorter tmax, higher Cmax and greater bioavailability than OTFC and is well tolerated. The dose proportionality of Cmax and AUC0-1 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.