Pulmonary administration of aerosolised fentanyl: Pharmacokinetic analysis of systemic delivery

Abstract

Aims: Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath- actuated, microprocessor-controlled metered dose oral inhaler (SmartMist(TM), Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain. Methods: Aersolised pulmonary fentanyl base 100-300 μg was administered to healthy volunteers using SmartMist(TM) and the resultant plasma concentration-time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects. Results: Plasma concentrations from SmartMist(TM) were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged ≃100%, and was > 50% within 5 min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose-dependence from either route. Side-effects (e.g. sedation, lightheadedness) were the same from both routes. Conclusions: Fentanyl delivery using SmartMist(TM) can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae.