Pharmacokinetics of fentanyl after subcutaneous administration in volunteers

Abstract

Background and objective: Pain relief using intermittent subcutaneous injections of an opioid (e.g. morphine) avoids the need for venous access and does not require complex or expensive pumps and devices. Although data on the pharmacokinetics of subcutaneous morphine exist, there are no comparable data for fentanyl in healthy volunteers. Therefore, the aim of this study was to characterize the pharmacokinetics of 200 μg fentanyl administered as a single bolus dose via the subcutaneous route in healthy opioid-naive volunteers. Methods: Nine healthy male volunteers were given 200 μg of subcutaneous fentanyl for more than 30 s. Opioid effects were blocked by administration of naltrexone. Venous blood samples taken at intervals from 5 min to 10 h after the dose were assayed using a liquid chromatography-mass spectrometry method. Pharmacokinetic data were analysed using a noncompartmental analysis approach. Results: After subcutaneous bolus dose administration, the median maximum concentration of fentanyl was 0.55 ng ml−1 (range 0.28–0.87 ng ml−1), reached at a median time of 15 min (range 10–30 min). The terminal half-life was 10.00 h (range 5.48–16.37 h). Conclusion: Absorption of subcutaneous fentanyl was relatively rapid and similar to the rate of absorption previously reported for subcutaneous morphine; the terminal half-life for fentanyl was substantially longer (10 h) than that of morphine (2.1 h), and blood concentrations were no more variable than that after administration by other nonintravenous routes.