Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery.
OBJECTIVE
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, Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain.


METHODS
Aersolised pulmonary fentanyl base 100-300 microg was administered to healthy volunteers using SmartMist 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 were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged approximately 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 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.
Department of Anaesthesia and Pain Management, University of Sydney at Royal North Shore Hospital, St Leonards, NSW, Australia.
L E
LE
Mather
A
A
Woodhouse
M E
ME
Ward
S J
SJ
Farr
R A
RA
Rubsamen
L G
LG
Eltherington
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009330:Nebulizers and Vaporizers; D010146:Pain / Q000188:drug therapy*
D000336:Aerosols; D000701:Analgesics, Opioid; D005283:Fentanyl