Skip to main content
SpringerLink
Log in

Bioavailability of dexmedetomidine after intranasal administration

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The aim of this proof-of-concept study was to characterize the pharmacokinetics and pharmacodynamics of intranasal dexmedetomidine compared with its intravenous administration in a small number of healthy volunteers.

Methods

Single doses of 84 μg of dexmedetomidine were given once intravenously and once intranasally to seven healthy men. Plasma dexmedetomidine concentrations were measured for 10 h, and pharmacokinetic variables were calculated with standard noncompartmental methods. Heart rate, blood pressure, concentrations of adrenaline and noradrenaline in plasma, and central nervous system drug effects (with the Maddox wing, Bispectral Index, and three visual analog scales) were monitored to assess the pharmacological effects of dexmedetomidine.

Results

Six individuals were included in the analyses. Following intranasal administration, peak plasma concentrations of dexmedetomidine were reached in 38 (15–60) min and its absolute bioavailability was 65% (35–93%) (medians and ranges). Pharmacological effects were similar with both routes of administration, but their onset was more rapid after intravenous administration.

Conclusions

Dexmedetomidine is rather rapidly and efficiently absorbed after intranasal administration. Compared with intravenous administration, intranasal administration may be a feasible alternative in patients requiring light sedation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Hayashi Y, Maze M (1993) Alpha 2 adrenoceptor agonists and anaesthesia. Br J Anaesth 71(1):108–118

    Article  PubMed  CAS  Google Scholar 

  2. Yuen VM, Irwin MG, Hui TW, Yuen MK, Lee LH (2007) A double-blind, crossover assessment of the sedative and analgesic effects of intranasal dexmedetomidine. Anesth Analg 105(2):374–380

    Article  PubMed  CAS  Google Scholar 

  3. Yuen VM, Hui TW, Irwin MG, Yuen MK (2008) A comparison of intranasal dexmedetomidine and oral midazolam for premedication in pediatric anesthesia: a double-blinded randomized controlled trial. Anesth Analg 106(6):1715–1721

    Article  PubMed  CAS  Google Scholar 

  4. Yuen VM, Hui TW, Irwin MG, Yao TJ, Wong GL, Yuen MK (2010) Optimal timing for the administration of intranasal dexmedetomidine for premedication in children. Anaesthesia 65(9):922–929

    Article  PubMed  CAS  Google Scholar 

  5. Guidance for Industry Bioanalytical Method Validation U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM) May 2001 BP http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070107.pdf

  6. Ji QC, Zhou JY, Gonzales RJ, Gage EM, El-Shourbagy TA (2004) Simultaneous quantitation of dexmedetomidine and glucuronide metabolites (G-Dex-1 and G-Dex-2) in human plasma utilizing liquid chromatography with tandem mass spectrometric detection. Rapid Commun Mass Spectrom 18(15):1753–1760

    Article  PubMed  CAS  Google Scholar 

  7. Scheinin M, Karhuvaara S, Ojala-Karlsson P, Kallio A, Koulu M (1991) Plasma 3, 4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are insensitive indicators of alpha 2-adrenoceptor mediated regulation of norepinephrine release in healthy human volunteers. Life Sci 49(1):75–84

    Article  PubMed  CAS  Google Scholar 

  8. Hannington-Kiff JG (1970) Measurement of recovery from outpatient general anaesthesia with a simple ocular test. Br Med J 3(5715):132–135

    Article  PubMed  CAS  Google Scholar 

  9. Sigl JC, Chamoun NG (1994) An introduction to bispectral analysis for the electroencephalogram. J Clin Monit 10(6):392–404

    Article  PubMed  CAS  Google Scholar 

  10. Bond A, Lader MH (1974) The use of visual analogue scales in rating subjective feelings. Br J Med Psychol 1974(47):211–218

    Google Scholar 

  11. Anttila M, Penttila J, Helminen A, Vuorilehto L, Scheinin H (2003) Bioavailability of dexmedetomidine after extravascular doses in healthy subjects. Br J Clin Pharmacol 56(6):691–693

    Article  PubMed  Google Scholar 

  12. Takala A, Kaasalainen V, Seppala T, Kalso E, Olkkola KT (1997) Pharmacokinetic comparison of intravenous and intranasal administration of oxycodone. Acta Anaesthesiol Scand 41(2):309–312

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Ms. Elina Kahra, Medical Laboratory Technologist, is acknowledged for skilful assistance in handling the blood samples. Ms. Teija Lemmetyinen, RN, is acknowledged for invaluable help in running the study days. This work was financially supported by Turku University Hospital research grants #13821 and #13388.

Conflict of Interest

Dr. Iirola, Dr. Aantaa and Dr. Olkkola have ongoing contract research relationships with Orion Corporation (Espoo, Finland), the original developer of dexmedetomidine. Dr. Iirola has received speaker fees from Orion Corporation (Espoo, Finland). Dr. Aantaa has been a paid consultant for Orion Corporation (Espoo, Finland) and Abbott Laboratories (Abbott Park, IL, USA), the original codevelopers of dexmedetomidine, as well as for Hospira (Lake Forest, IL, USA). Hospira has a license agreement with Orion Corporation concerning dexmedetomidine (Precedex®). Dr. Lahtinen has been engaged in contract research for Orion Corporation (Espoo, Finland). The laboratory of Dr. Scheinin has contract research relationships with Orion Corporation (Espoo, Finland) and Hospira (Lake Forest, IL, USA). Hospira has a license agreement with Orion Corporation concerning dexmedetomidine (Precedex®). Dr Scheinin has also received speaker fees and consulting fees from Orion Corporation.

Author information

Authors and Affiliations

  1. Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku and Turku University Hospital, P.O. Box 52, FI-20521, Turku, Finland

    Timo Iirola, Sanna Vilo, Tuula Manner, Riku Aantaa & Klaus T. Olkkola

  2. Department of Pharmacology, Drug Development and Therapeutics, University of Turku and Unit of Clinical Pharmacology, TYKSLAB, Turku, Finland

    Maria Lahtinen & Mika Scheinin

Authors
  1. Timo Iirola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sanna Vilo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tuula Manner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Riku Aantaa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Lahtinen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mika Scheinin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Klaus T. Olkkola
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Timo Iirola.

Additional information

Dr. Iirola and Dr. Vilo share equal contribution.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iirola, T., Vilo, S., Manner, T. et al. Bioavailability of dexmedetomidine after intranasal administration. Eur J Clin Pharmacol 67, 825–831 (2011). https://doi.org/10.1007/s00228-011-1002-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-011-1002-y

Keywords

Search

Navigation