Multiple dose pharmacokinetics and pharmacodynamics of inhaled liposomeencapsulated fentanyl (LEF)

Inhaled LEF can provide a sustained plasma opioid concentration suitable for pain management. This study was designed to assess the pharmacokinetics and respiratory effects following multiple dose administration in healthy volunteers. Following the application of a non-invasive respiratory function monitor (Respitrace™) and pulse oximeter, 5 doses of 5ml of LEF (0.8 mg.ml^-1 fentanyl) were administered pulmonarily to 6 subjects (5M/1F) at 12 hr intervals. Respiratory function was monitored continuously during the study. Venous blood was collected regularly for 72 hrs to determine plasma fentanyl concentration (Cf). Peak Cf (2.27±0.55 ng.ml-1) occurred at 15 min. The Cfs were maintained within therapeutic analgesic levels throughout the study (2.27 to 0.55 ng.ml^-1). Oxygen saturations were above 92%, and respiratory rates, tidal volumes and minute ventilations were maintained within 10-20% of baseline throughout the study. These findings suggest that LEF can provide adequate analgesia with minimal risk of respiratory depression. Future clinical studies are necessary to determine its efficacy and safety in different patient populations for pain management.