Faster absorption and higher systemic bioavailability of intranasal fentanyl spray compared to oral transmucosal fentanyl citrate in healthy subjects

Author： Nave Ruediger

Publisher： Informa Healthcare

ISSN： 1521-0464

Source： Drug Delivery, Vol.20, Iss.5, 2013-06, pp. : 216-223

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Abstract

Abstract Context: 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).Materials and 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.Discussion and conclusion: One dose of INFS gives significantly higher plasma fentanyl levels and significantly higher bioavailability than OTFC based on dose-normalized AUC.