• Ruediger Nave, Holger Schmitt, and Lars Popper.
• Nycomed a Takeda Company, Konstanz, Germany.
• Drug Deliv. 2013 Jun 1; 20 (5): 216-23.

ContextIntranasal fentanyl spray (INFS) was developed for the treatment of breakthrough pain in cancer patients using an alternative route of administration.ObjectiveThe aim of this clinical study was to investigate the pharmacokinetic (PK) profile and bioavailability of INFS in healthy subjects compared to oral transmucosal fentanyl citrate (OTFC).Materials And MethodsIn a randomized, single-center, open-label, two-way crossover PK study, 24 subjects (12 male, 12 female, mean age 25.2 years) received INFS (single-dose delivery system 200 μg/100 μl) and OTFC (buccal lozenge, 200 µg). Naltrexone was given to prevent potential adverse reactions. Frequent plasma samples were taken up to 96 h and analyzed by LC-MS/MS with a lower limit of quantitation of 25 pg/ml. Primary PK parameter was the area under the fentanyl plasma concentration-time curve (AUC(0-inf)).ResultsCompared to OTFC, a much faster absorption rate was observed for INFS which was supported by the much earlier appearance of detectable fentanyl plasma levels and a shorter T(max). At 15 min post-dose, the mean plasma fentanyl levels reached 602 pg/ml for INFS and 29 pg/ml for OTFC. Significantly higher C(max) and AUC values were obtained with INFS compared to OTFC. Although administered for 15 min, consumption of OTFC was incomplete in many incidences (∼70%) upon visual inspection. No safety concerns were identified for fentanyl administration in combination with oral naltrexone.Discussion And ConclusionOne dose of INFS gives significantly higher plasma fentanyl levels and significantly higher bioavailability than OTFC based on dose-normalized AUC.

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