G5 Doctoral dissertation (article)

Pharmacokinetics and effects of extravascularly administered dexmedetomidine : studies on pediatric and adult patients, and healthy adult volunteers




List of Authors: Uusalo Panu

Publisher: University of Turku

Place: Turku

Publication year: 2019

ISBN: 978-951-29-7774-1

eISBN: 978-951-29-7775-8

URL: http://urn.fi/URN:ISBN:978-951-29-7775-8


Abstract

Patients undergoing surgery and other invasive procedures need sedation and pain relief. Many unpleasant sensations and experiences can be reduced by administration of conventional sedative and analgesic drugs, but most of these compounds are associated with troublesome adverse effects such as respiratory depression and nausea.

Dexmedetomidine is a relatively new drug that acts by activating α2-adrenoceptors. It has received marketing authorisation for intensive care sedation and for procedural sedation of adult patients. In addition to its sedative property, dexmedetomidine exerts analgesic and antiemetic effects. In comparison to other analgesic and sedative agents, dexmedetomidine has minimal effects on respiration.

Dexmedetomidine has been developed and approved for intravenous administration. Several reports exist on the use of intranasal and other extravascular routes of administration of dexmedetomidine. Nonetheless, the pharmacokinetic and pharmacodynamic properties of extravascularly administered dexmedetomidine have remained poorly characterized. The intranasal route of administration appears to be feasible for administration of dexmedetomidine to children, but there is rather little information available about the pharmacokinetics of dexmedetomidine in children.

In the present series of studies, the pharmacokinetics and -dynamics of subcutaneously and intranasally administered dexmedetomidine were characterized in healthy volunteers and in pediatric patients. We also evaluated the anesthetic sparing effect of intranasally administered dexmedetomidine in pediatric patients undergoing ambulatory sedation, and the analgesic sparing effect of intranasally administered dexmedetomidine in adult patients undergoing hip arthroplasty under general anesthesia.

The systemic bioavailability of subcutaneously administered dexmedetomidine was good (81%), but interindividual variation was large. After intranasal administration of dexmedetomidine in pediatric patients, on average the peak plasma concentrations were achieved in 37 minutes, with peak effects normally observed at 45 minutes. Peak concentrations and exposure to the study drug decreased with age. Intranasal doses of 2-3 μg/kg achieved clinically acceptable sedation in about 94% of pediatric patients undergoing magnetic resonance imaging. In adult patients undergoing total hip arthroplasty, the use of intranasal low-dose dexmedetomidine decreased postoperative opioid consumption in a clinically significant manner.

Our findings provide support for the use of intranasal dexmedetomidine in pediatric patients requiring light or moderate sedation and in adult patients undergoing painful surgical procedures. Subcutaneous administration of dexmedetomidine appears promising e.g. for patients needing palliative sedation and analgesia, but further studies are warranted to confirm this proposal.


Last updated on 2021-24-06 at 09:15