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 mg 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.

Orally administered ethyl alcohol (1 ml/kg of 100% ethyl alcohol + 1 ml/kg tonic water) (the equivalent of two cocktails) produced tolerance to experimentally induced pain comparable to 0.17 mg/kg s.q. morphine (11.6 mg in a 70 kg person) [corrected]. Pain threshold, i.e., the initial awareness of pain, was not modified by either morphine or alcohol. The experiment was run using 18 paid subjects in an experimenter-blinded design. Both a pharmacologically active placebo (atropine) as well as a totally inactive placebo (saline) were employed. Pain induction occurred via mechanical pressure on the Achilles tendon utilizing a device previously standardized in the clinical screening of over 100,000 patients for pain awareness. These results suggest that alcohol, in non-intoxicating quantities, may be an effective adjunct to other analgesic modalities.

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