1. ¹Depts. of Anesthesia and Pharmacology, Dalhousie U., Halifax, NS and DELEX Therapeutics Inc., Mississauga, ON, Canada
2. |[ast]|Ventana Clinical Research Corporation, Toronto, ON.

Abstract

After obtaining IND and IRB approval and informed consent, a Phase Ib study was conducted to evaluate the safety, pharmacokinetics, and pharmacodynamics (as measured by pupillometry) of AeroLEF|[trade]|. On two separate occasions, 6 healthy volunteers were administered 200 |[mu]|g of intravenous (iv) fentanyl and AeroLEF|[trade]| (1500 |[mu]|g fentanyl base) via a breath actuated nebulizer, Aero-Eclipse|[trade]|. The mean (|[plusmn]|SD) C_max and T_max of fentanyl concentrations (C_f) were 1.46 |[plusmn]| 0.83 ng/ml and 0.39 |[plusmn]| 0.32 hr following AeroLEF|[trade]|, compared to 1.76 |[plusmn]| 1.19 ng/ml and 0.1 |[plusmn]| 0.03 hr respectively for iv fentanyl. The mean (|[plusmn]|SD) bioavail-ability was 22.2 |[plusmn]| 9.3% for AeroLEF|[trade]|. The mean (|[plusmn]|SD) total duration of C_f |[ge]| 0.5 ng/ml (for therapeutic analgesia) was 3.78 |[plusmn]| 1.92 hr for AeroLEF|[trade]| compared to 0.86 |[plusmn]| 0.39 hr for iv fentanyl. The time course of pupillometry effects tracked closely with C_f, with maximum constriction observed near C_max. Oxygen saturation, respiratory rates, and hemodynamics were within normal limits throughout the study. These data suggest that AeroLEF|[trade]| can provide a rapid onset and prolonged analgesia compared to iv fentanyl. Future clinical trials will be conducted to determine AeroLEF|[trade]| safety and efficacy in patients with acute or cancer breakthrough pain.