title: Inhaled fentanyl aerosol in healthy volunteers: pharmacokinetics and pharmacodynamics.
abstract: BACKGROUND
  Rapid delivery of potent opioid to the systemic circulation is an important feature for the effective treatment of acute and acute-on-chronic breakthrough pain. The delivery of different opioids by the pulmonary route has been inconsistent, usually resulting in low bioavailability of the drug. Staccato® Fentanyl for Inhalation is a handheld inhaler producing a single metered dose of aerosolized fentanyl during a single inspiration. The aerosol is of high purity (≥98%) at a particle size (1 to 3.5 microns) shown to be best for pulmonary absorption.
  
  
  METHODS
  We conducted the study in healthy volunteers in 2 stages. In the crossover stage, 10 subjects received IV fentanyl 25 µg and inhaled fentanyl 25 µg on separate occasions. The dose escalation stage was a multidose, randomized, double-blind, placebo-controlled, single-period dose escalation study of inhaled fentanyl (50 to 300 µg). Serial blood sampling was performed over an 8-hour period after drug administration to determine the pharmacokinetic profile, and serial pupillometry was performed as a measure of pharmacodynamic effect.
  
  
  RESULTS
  In the crossover stage the pharmacokinetic profiles of the inhaled and IV fentanyl showed similar peak arterial concentrations and areas under the curve. The time to maximum concentration was slightly shorter for the inhaled than IV fentanyl, 20.5 and 31.5 seconds, respectively. In the dose escalation stage the administration of repeated doses resulted in predictable, dose-dependent serum concentrations.
  
  
  CONCLUSIONS
  This study has demonstrated that the pharmacokinetic profile of single doses of inhaled fentanyl is comparable to IV administration.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA. david.macleod@duke.edu
authors.forename: David B
authors.initials: DB
authors.lastname: Macleod
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Habib
authors.forename: Keita
authors.initials: K
authors.lastname: Ikeda
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Spyker
authors.forename: James V
authors.initials: JV
authors.lastname: Cassella
authors.forename: Kok Yuen
authors.initials: KY
authors.lastname: Ho
authors.forename: Tong J
authors.initials: TJ
authors.lastname: Gan
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D015331:Cohort Studies; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000336:Aerosols; D005283:Fentanyl