• A Li, V M Yuen, S Goulay-Dufaÿ, Y Sheng, J F Standing, P C L Kwok, LeungM K MMKMDepartment of Anaesthesiology, Queen Mary Hospital, Hong Kong., A S Leung, WongI C KICKDepartment of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong., and M G Irwin.
• Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong.
• Br J Anaesth. 2018 May 1; 120 (5): 960-968.

BackgroundIntranasal dexmedetomidine produces safe, effective sedation in children and adults. It may be administered by drops from a syringe or by nasal mucosal atomisation (MAD NasalTM).MethodsThis prospective, three-period, crossover, double-blind study compared the pharmacokinetic (PK) and pharmacodynamic (PD) profile of i.v. administration with these two different modes of administration. In each session each subject received 1 μg kg-1 dexmedetomidine, either i.v., intranasal with the atomiser or intranasal by drops. Dexmedetomidine plasma concentration and Ramsay sedation score were used for PK/PD modelling by NONMEM.ResultsThe i.v. route had a significantly faster onset (15 min, 95% CI 15-20 min) compared to intranasal routes by atomiser (47.5 min, 95% CI 25-135 min), and by drops (60 min, 95%CI 30-75 min), (P<0.001). There was no significant difference in sedation duration across the three treatment groups (P=0.88) nor in the median onset time between the two modes of intranasal administration (P=0.94). A 2-compartment disposition model, with transit intranasal absorption and clearance driven by cardiac output using the well-stirred liver model, was the final PK model. Intranasal bioavailability was estimated to be 40.6% (95% CI 34.7-54.4%) and 40.7% (95% CI 36.5-53.2%) for atomisation and drops respectively. Sedation score was modelled via a sigmoidal Emax model driven by an effect compartment. The effect compartment had an equilibration half time 3.3 (95% CI 1.8-4.7) min-1, and the EC50 was estimated to be 903 (95% CI 450-2344) pg ml-1.ConclusionsThere is no difference in bioavailability with atomisation or nasal drops. A similar degree of sedation can be achieved by either method.Clinical Trial RegistrationHKUCTR-1617.Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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