Pharmacokinetics and pharmacodynamics of intravenous medetomidine in the horse

Kristin N. Grimsrud, Khursheed R. Mama, Eugene P. Steffey, Scott D. Stanley

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Objective To describe the pharmacodynamics and pharmacokinetics following an intravenous (IV) bolus dose of medetomidine in the horse. Study design Prospective experimental trial. Animals Eight, mature healthy horses age 11.7±4.6 (mean±SD) years, weighing 557±54kg. Methods Medetomidine (10μgkg-1) was administered IV. Blood was sampled at fixed time points from before drug administration to 48hours post administration. Behavioral, physiological and biochemical data were obtained at predetermined time points from 0minutes to 24hours post administration. An algometer was also used to measure threshold responses to noxious stimuli. Medetomidine concentrations were determined by liquid chromatography-Mass Spectrometry and used for calculation of pharmacokinetic parameters using noncompartmental and compartmental analysis. Results Pharmacokinetic analysis estimated that medetomidine peaked (8.86±3.87ngmL-1) at 6.4±2.7minutes following administration and was last detected at 165±77minutes post administration. Medetomidine had a clearance of 39.6±14.6mLkg-1minute-1 and a volume of distribution of 1854±565mLkg-1. The elimination half-life was 29.1±12.5minutes. Glucose concentration reached a maximum of 176±46mgdL-1 approximately 1hour post administration. Decreased heart rate, respiratory rate, borborygmi, packed cell volume, and total protein concentration were observed following administration. Horses lowered their heads from 107±12 to 20±10cm within 10minutes of drug administration and gradually returned to normal. Horse mobility decreased after drug administration. An increased mechanical threshold was present from 10 to 45minutes and horses were less responsive to sound. Conclusion and clinical relevance Behavioral and physiological effects following intravenous administration positively correlate with pharmacokinetic profiles from plasma medetomidine concentrations. Glucose concentration gradually transiently increased following medetomidine administration. The analgesic effect of the drug appeared to have a very short duration.

Original languageEnglish
Pages (from-to)38-48
Number of pages11
JournalVeterinary Anaesthesia and Analgesia
Volume39
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Horse
  • Medetomidine
  • Pharmacodynamics
  • Pharmacokinetics
  • Sedation

ASJC Scopus subject areas

  • Veterinary (all)

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