e20554 Background: The nasal route offers the ability to enhance fentanyl delivery and better match the rapid onset and short duration (30–60 min) of breakthrough cancer pain compared with standard oral delivery. However, conventional nasal fentanyl solutions can be associated with variable, and sometimes supratherapeutic maximum plasma concentrations (Cmax). To optimise rapid absorption and delivery, three novel nasal spray formulations have been developed: fentanyl pectin nasal spray (FPNS), fentanyl chitosan nasal spray (FChNS), and fentanyl in chitosan-poloxamer 188 solute (FChP). Methods: This phase I, open-label, crossover study was conducted in 18 healthy adult volunteers to compare the pharmacokinetic profiles of the three new nasal fentanyl formulations with oral transmucosal fentanyl citrate (OTFC). Subjects were dosed on four occasions, separated by a >3-day washout period, under naltrexone blockade, with the nasal sprays (each containing fentanyl citrate 100μg in 100μL) and OTFC 200μg according to a randomized sequence. Venous plasma fentanyl concentrations were measured before and up to 24 hours post-dose. Local nasal tolerability was assessed by a clinician and a reactogenicity questionnaire. Results: Compared with OTFC, mean AUCs∞ for all three nasal sprays were significantly higher (P<0.05) and bioavailability significantly greater (FPNS 132%; FChNS 154%, FChP 122%). Median tmax (FPNS 19.8min; FChNS 10.2min, FChP 15.6min) were significantly (P<0.001) reduced (OTFC 90min) and mean Cmax significantly increased with all nasal sprays compared with OTFC. Of the three nasal sprays, FPNS had the lowest nasal reactogenicity symptom incidence. Conclusions: Compared with OTFC, all three fentanyl nasal spray formulations demonstrated enhanced pharmacokinetic profiles appropriate for breakthrough cancer pain as evidenced by significantly increased systemic exposure and reduced times to peak plasma values. FPNS exhibited the most favourable tolerability profile. [Table: see text]
Safety and efficacy of oral transmucosal fentanyl citrate compared to morphine sulphate immediate release tablet in management of breakthrough cancer pain
