title: Faster absorption and higher systemic bioavailability of intranasal fentanyl spray compared to oral transmucosal fentanyl citrate in healthy subjects.
abstract: BACKGROUND
  Intranasal fentanyl spray (INFS) was developed for the treatment of breakthrough pain in cancer patients using an alternative route of administration.
  
  
  OBJECTIVE
  The 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).
  
  
  METHODS
  In 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)).
  
  
  RESULTS
  Compared 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.
  
  
  CONCLUSIONS
  One dose of INFS gives significantly higher plasma fentanyl levels and significantly higher bioavailability than OTFC based on dose-normalized AUC.
authors: Nycomed a Takeda Company, Konstanz, Germany.
authors: Ruediger
authors: R
authors: Nave
authors: Holger
authors: H
authors: Schmitt
authors: Lars
authors: L
authors: Popper
mesh_terms: D000042:Absorption; D000278:Administration, Buccal; D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D008297:Male
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl