Safety, pharmacokinetics, and pharmacodynamics of Dexmedetomidine two-phase flow atomization in healthy subjects: a randomized, parallel study.

Background: In this study, we aimed to compare the sedative effects, pharmacokinetics (PKs), and safety of dexmedetomidine (DEX) administered using a two-phase flow atomization device with those of conventional intranasal drop-based administration in healthy volunteers.

Methods: This prospective, parallel, double-blind study compared the PK and pharmacodynamic (PD) profiles of DEX administered via conventional intranasal drop (Group C) or two-phase flow atomization (Group E). Twenty-two healthy adult volunteers were enrolled and randomly assigned to the two groups using a computer-generated randomization sequence. Each participant received DEX at a dose of 2 µg/kg. Sedation was assessed using the Ramsay Sedation Scale and the bispectral index, and PK analysis was performed on blood samples collected at multiple time points.

Results: The two-phase flow atomization group exhibited a significantly faster onset of sedation than the conventional intranasal drop-based administration group and a longer duration of sedation. Compared with Group C, Group E presented an increasing trend in the maximum plasma concentration and in the area under the concentration‒time curve from time zero to the last time point (AUC0t). We found no significant differences in other PK parameters between the two groups, with all P-values > 0.05. The plasma concentrations were slightly higher in the two-phase flow atomization group after 30 min. The changes in systolic blood pressure and heart rate of both groups of volunteers were within 25% of the baseline values, with no adverse reactions such as hypotension or sinus bradycardia. CONCLUSIONS : The findings indicate that the two-phase flow atomization device offers faster onset and longer duration of sedation with DEX nasal administration, with a favorable safety profile in healthy volunteers (American Society of Anesthesiologists Physical Status Class 1) under specific conditions. Therefore, based on the sedation dynamics, we infer that this device may enhance drug deposition in the olfactory region of the nasal cavity, thereby enhancing the effects of the drug in the central nervous system through nose-to-brain delivery. This study provides new insights into the optimization of nasal drug delivery devices, particularly for pediatric patients and patients in clinical settings requiring rapid sedation.

Trial registration: This study was registered at ChiCTR.org.cn (registration number ChiCTR2400091480) on 29/10/2024.