No 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 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.

Pulmonary delivery of aqueous bolus aerosols of insulin in healthy subjects resulted in rapid absorption with an associated hypoglycemic effect quicker than is achieved after subcutaneous dosing of regular insulin. Inhaled insulin pharmacokinetics and pharmacodynamics were independent of formulation variables (pH, concentration) but affected by certain respiratory maneuvers.

Our previous study suggested that when compared between patients, morphine, pethidine and fentanyl were equally satisfactory for use in patient-controlled analgesia (PCA), although quantitative differences in their side-effect profiles were detectable. The present study evaluated whether individual patients could detect differences or express preferences for individual opioids when treated by PCA with all three in random sequence finishing with the first administered opioid. The main side effects were pruritus, nausea and vomiting. There were few differences in patients' responses to morphine, pethidine and fentanyl, or of satisfaction with these drugs, across patients, but individual patients' responses to the opioids could be highly variable. Some patients were able to tolerate all three opioids investigated, some were intolerant to all and some patients appeared to be sensitive to one or two of the opioids but show a preference for the remainder. These findings support the clinical practice of changing from one opioid to another (with good effect) in post-operative patients experiencing intolerable side-effects. The reasons for a patient responding differently to different opioids and even to the same opioid on separate occasions are not clear and appear inexplicable on the grounds of currently postulated receptor affinities or of physicochemical properties of the opioids studied. A plethora of factors will influence how an individual patient will respond to surgery and how he/she will recover. The physiological response to opioids is one variable which appears to be influenced by this complex set of factors and in turn will affect them. The findings of this study, like that of its predecessor, suggest that morphine, pethidine and fentanyl can be used successfully in PCA and that for some patients who are responding poorly, changing the opioid may be beneficial.