title: Impact of allergic rhinitis and its treatment on the pharmacokinetics of nasally administered fentanyl.
abstract: OBJECTIVE
  Fentanyl pectin nasal spray (FPNS, Lazanda® in the US and PecFent® in Europe and Australia) is a novel analgesic approved for the management of breakthrough pain in cancer patients. Given that the fentanyl is nasally administered, it is important to understand whether concomitant allergic rhinitis, or its treatment with a vasoconstrictor, would affect its absorption and, potentially, its efficacy or safety.
  
  
  METHODS
  Subjects with a history of allergic rhinitis were screened to identify subjects who developed at least moderate rhinitis symptoms on exposure to pollen allergen (either ragweed or tree) in an environmental exposure chamber (EEC). These were entered into a randomized, three-way crossover study in which each subject received 100 μg of FPNS under three exposure conditions; Control (no rhinitis), Rhinitis (symptomatic without decongestant), Treated (symptomatic with concomitant oxymetazoline). Blood samples for fentanyl were collected over a 24-hour period.
  
  
  RESULTS
  A total of 132 subjects was screened to identify 54 for inclusion in the study; 31 were evaluable for pharmacokinetics. Measures of fentanyl absorption (mean or median) were similar between Control and Rhinitis conditions: Cmax 453.0 vs. 467.8 pg/ml; AUCt 1,292.3 vs. 1,325.4 pg×h/ml, AUC0-∞ 1,430.6 vs. 1,387 pg×h/ml and tmax 20 vs. 17 minutes. When oxymetazoline was co-administered, overall fentanyl absorption was slightly reduced (AUC0-∞ 1,362.4 pg×h/ml); but, more clinically relevant were the delayed rate of absorption (tmax 53 minutes) and reduced Cmax (235.3 pg/ml).
  
  
  CONCLUSIONS
  Patients treated with FPNS will be unaffected by the development of allergic rhinitis; but, if oxymetazoline is prescribed, the patient would benefit from added supervision when oxymetazoline is started and stopped.
authors: ARchimedes Development Limited, Albert Einstein Centre, Nottingham Science and Technology Park, Nottingham, UK.
authors: Michael
authors: M
authors: Perelman
authors: Anthony N
authors: AN
authors: Fisher
authors: Alan
authors: A
authors: Smith
authors: Alastair
authors: A
authors: Knight
mesh_terms: D000042:Absorption; D000281:Administration, Intranasal; D000328:Adult; D000336:Aerosols; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D014663:Nasal Decongestants / Q000009:adverse effects / Q000627:therapeutic use*; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D010109:Oxymetazoline / Q000009:adverse effects / Q000627:therapeutic use*; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy*; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000336:Aerosols; D000701:Analgesics, Opioid; D014663:Nasal Decongestants; D014662:Vasoconstrictor Agents; D010109:Oxymetazoline; D005283:Fentanyl