Safety and pharmacokinetics of inhaled morphine delivered using the AERx system in patients with moderate-to-severe asthma

Int J Clin Pharmacol Ther. 2004 Aug;42(8):456-62. doi: 10.5414/cpp42456.


Objective: The safety and pharmacokinetics of inhaled morphine in asthmatic subjects were investigated using the AERx System, a novel aerosol system.

Methods: Twenty subjects with asthma received inhaled placebo and inhaled morphine sulfate, 2.2 mg, 4.4 mg and 8.8 mg, on separate days in a single-blind crossover study. Six of the subjects received an additional open-label dose of 17.6 mg on a separate day. Plasma morphine concentrations and safety evaluations including pulmonary function testing were performed.

Results: Mean tmax values were similar following all dose groups at approximately 1-2 minutes. Mean AUC(0-->1) values showed dose proportionality for the first 3 dose groups (6.3, 12.3 and 24.3 ng x h x ml(-1)), the mean AUC(0-->1) for the 17.6 mg dose group was 1.6x that of the 8.8 mg dose group. No statistically significant differences in forced expiratory volume in 1 sec (FEV1) were found for the 2.2 mg, 4.4 mg, or 8.8 mg dose groups; at 17.6 mg, a statistically significant but not clinically meaningful reduction in mean FEV1 (-8.18%) from baseline occurred at 10 minutes compared to placebo, spontaneously returning to baseline by 60 min. Four subjects experienced significant but reversible decreases in FEV1 of > or = 20% compared to baseline and across all dose levels including after placebo, but with no associated increase in dyspnea, wheezing or other adverse events.

Conclusions: Inhaled morphine using the AERx System was absorbed rapidly and demonstrated dose-dependent plasma concentrations. It was well-tolerated and did not cause clinically significant bronchoconstriction in most subjects with moderate-to-severe asthma.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Administration, Inhalation
  • Anti-Asthmatic Agents* / administration & dosage
  • Anti-Asthmatic Agents* / adverse effects
  • Anti-Asthmatic Agents* / pharmacokinetics
  • Anti-Asthmatic Agents* / therapeutic use
  • Area Under Curve
  • Asthma / drug therapy*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems / instrumentation*
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Morphine* / administration & dosage
  • Morphine* / adverse effects
  • Morphine* / pharmacokinetics
  • Morphine* / therapeutic use
  • Severity of Illness Index
  • Single-Blind Method


  • Anti-Asthmatic Agents
  • Morphine