No abstract

8629 Background: Cancer patients frequently experience breakthrough pain which is a transitory flare of moderate or severe pain occurring on top of otherwise controlled, persistent pain. Fentanyl TAIFUN (FT), a novel breath-actuated dry powder inhaler is being developed for the treatment of breakthrough cancer pain in patients with ongoing opiate therapy. Methods: A randomized, open-label, crossover phase I study with 5 periods derived pharmacokinetics after fentanyl oromucosal (Actiq, A) and pulmonary (FT) administration in 30 healthy volunteers. Each single dose of study medication (200 mcg A; or 100, 200, 400 or 800 mcg FT) was administered following premedication with 50 mg of naltrexone with a minimum of 7 days between doses. Pharmacokinetic parameters were calculated from the plasma concentrations using a non-compartmental model. Results: The plasma concentrations of FT increased proportionally to the increasing dose and t1/2 was independent of the dose. FT had a linear elimination phase. FT had a substantially faster absorption and higher peak fentanyl concentration (Cmax) than A. Median Tmax was 1 and 60 min for FT and A, respectively. Moreover, there was an 8-fold increase in bioavailability of fentanyl during the first 20 min when 200 mcg FT is compared to 200 mcg A. Conclusions: The plasma concentrations from FT increases proportionally to the increasing dose while t1/2 is independent of the dose, and there is a linear elimination phase. Overall, FT is substantially more bioavailable than A during the important first 20–30 minutes after administration. Inhalation of FT allows an immediate and comparable availability of fentanyl suggesting potential for rapid pain relief. [Table: see text] [Table: see text]