Pharmacokinetic profile in relation to anaesthesia characteristics after a 5 micellar microemulsion of propofol in the horse

P. Boscan, M. L. Rezende, Kristin N Grimsrud, Scott D Stanley, K. R. Mama, Eugene Steffey

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

BackgroundTo define the pharmacokinetic profile of propofol 5 microemulsion formulation in horses.MethodsFirst, propofol was administered as bolus injection (2 mg kg-1) to six xylazine-sedated horses. Secondly, after sedation and bolus injection, propofol was maintained with continuous infusion for 3 h [8.1 (sd 3.2) mg kg-1 h-1] to the same six horses. Thirdly, in two horses, a commercial propofol was used for comparison. Response to noxious stimulation was used to evaluate analgesia. Venous blood samples were obtained to measure propofol plasma concentration using liquid chromatography-mass spectrometry analysis. The plasma concentrations were related to the anaesthesia characteristics to determine the ED50.ResultsThe pharmacokinetic profile of propofol is best characterized by a non-compartmental model. The mean (confidence interval) for area under plasma concentration-time curve, elimination half-life, mean residence time, and clearance was 41 min g ml-1 (±7.7), 44.8 min (±21.3), 13.7 min (±3.2), and 45.8 ml min-1 kg-1 (±6.5), respectively. Linear regression analysis showed a correlation between plasma concentration and infusion rate (r2=0.47). Most propofol infusion rates did not inhibit the response to noxious stimulation and rates above 11.9 mg kg-1 h-1 caused involuntary muscle contractions. Better recoveries were associated with lower propofol plasma concentrations. Propofol plasma concentration frequently increased when horses woke from anaesthesia. ConclusionsCaution is warranted when propofol is used for continuous infusion due to variable kinetics, myoclonal activity, poor analgesia, and less desirable recovery quality.

Original languageEnglish (US)
Pages (from-to)330-337
Number of pages8
JournalBritish Journal of Anaesthesia
Volume104
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

Propofol
Horses
Anesthesia
Pharmacokinetics
Analgesia
Xylazine
Injections
Muscle Contraction
Liquid Chromatography
Smooth Muscle
Half-Life
Linear Models
Mass Spectrometry
Regression Analysis
Confidence Intervals

Keywords

  • Emulsifiers
  • Formulations
  • Horse
  • Pharmacokinetics
  • Pharmacolgy
  • Propofol

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

@article{29830fe5abfb46fc881e2409958f1b18,
title = "Pharmacokinetic profile in relation to anaesthesia characteristics after a 5 micellar microemulsion of propofol in the horse",
abstract = "BackgroundTo define the pharmacokinetic profile of propofol 5 microemulsion formulation in horses.MethodsFirst, propofol was administered as bolus injection (2 mg kg-1) to six xylazine-sedated horses. Secondly, after sedation and bolus injection, propofol was maintained with continuous infusion for 3 h [8.1 (sd 3.2) mg kg-1 h-1] to the same six horses. Thirdly, in two horses, a commercial propofol was used for comparison. Response to noxious stimulation was used to evaluate analgesia. Venous blood samples were obtained to measure propofol plasma concentration using liquid chromatography-mass spectrometry analysis. The plasma concentrations were related to the anaesthesia characteristics to determine the ED50.ResultsThe pharmacokinetic profile of propofol is best characterized by a non-compartmental model. The mean (confidence interval) for area under plasma concentration-time curve, elimination half-life, mean residence time, and clearance was 41 min g ml-1 (±7.7), 44.8 min (±21.3), 13.7 min (±3.2), and 45.8 ml min-1 kg-1 (±6.5), respectively. Linear regression analysis showed a correlation between plasma concentration and infusion rate (r2=0.47). Most propofol infusion rates did not inhibit the response to noxious stimulation and rates above 11.9 mg kg-1 h-1 caused involuntary muscle contractions. Better recoveries were associated with lower propofol plasma concentrations. Propofol plasma concentration frequently increased when horses woke from anaesthesia. ConclusionsCaution is warranted when propofol is used for continuous infusion due to variable kinetics, myoclonal activity, poor analgesia, and less desirable recovery quality.",
keywords = "Emulsifiers, Formulations, Horse, Pharmacokinetics, Pharmacolgy, Propofol",
author = "P. Boscan and Rezende, {M. L.} and Grimsrud, {Kristin N} and Stanley, {Scott D} and Mama, {K. R.} and Eugene Steffey",
year = "2010",
month = "3",
doi = "10.1093/bja/aep377",
language = "English (US)",
volume = "104",
pages = "330--337",
journal = "British Journal of Anaesthesia",
issn = "0007-0912",
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number = "3",

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TY - JOUR

T1 - Pharmacokinetic profile in relation to anaesthesia characteristics after a 5 micellar microemulsion of propofol in the horse

AU - Boscan, P.

AU - Rezende, M. L.

AU - Grimsrud, Kristin N

AU - Stanley, Scott D

AU - Mama, K. R.

AU - Steffey, Eugene

PY - 2010/3

Y1 - 2010/3

N2 - BackgroundTo define the pharmacokinetic profile of propofol 5 microemulsion formulation in horses.MethodsFirst, propofol was administered as bolus injection (2 mg kg-1) to six xylazine-sedated horses. Secondly, after sedation and bolus injection, propofol was maintained with continuous infusion for 3 h [8.1 (sd 3.2) mg kg-1 h-1] to the same six horses. Thirdly, in two horses, a commercial propofol was used for comparison. Response to noxious stimulation was used to evaluate analgesia. Venous blood samples were obtained to measure propofol plasma concentration using liquid chromatography-mass spectrometry analysis. The plasma concentrations were related to the anaesthesia characteristics to determine the ED50.ResultsThe pharmacokinetic profile of propofol is best characterized by a non-compartmental model. The mean (confidence interval) for area under plasma concentration-time curve, elimination half-life, mean residence time, and clearance was 41 min g ml-1 (±7.7), 44.8 min (±21.3), 13.7 min (±3.2), and 45.8 ml min-1 kg-1 (±6.5), respectively. Linear regression analysis showed a correlation between plasma concentration and infusion rate (r2=0.47). Most propofol infusion rates did not inhibit the response to noxious stimulation and rates above 11.9 mg kg-1 h-1 caused involuntary muscle contractions. Better recoveries were associated with lower propofol plasma concentrations. Propofol plasma concentration frequently increased when horses woke from anaesthesia. ConclusionsCaution is warranted when propofol is used for continuous infusion due to variable kinetics, myoclonal activity, poor analgesia, and less desirable recovery quality.

AB - BackgroundTo define the pharmacokinetic profile of propofol 5 microemulsion formulation in horses.MethodsFirst, propofol was administered as bolus injection (2 mg kg-1) to six xylazine-sedated horses. Secondly, after sedation and bolus injection, propofol was maintained with continuous infusion for 3 h [8.1 (sd 3.2) mg kg-1 h-1] to the same six horses. Thirdly, in two horses, a commercial propofol was used for comparison. Response to noxious stimulation was used to evaluate analgesia. Venous blood samples were obtained to measure propofol plasma concentration using liquid chromatography-mass spectrometry analysis. The plasma concentrations were related to the anaesthesia characteristics to determine the ED50.ResultsThe pharmacokinetic profile of propofol is best characterized by a non-compartmental model. The mean (confidence interval) for area under plasma concentration-time curve, elimination half-life, mean residence time, and clearance was 41 min g ml-1 (±7.7), 44.8 min (±21.3), 13.7 min (±3.2), and 45.8 ml min-1 kg-1 (±6.5), respectively. Linear regression analysis showed a correlation between plasma concentration and infusion rate (r2=0.47). Most propofol infusion rates did not inhibit the response to noxious stimulation and rates above 11.9 mg kg-1 h-1 caused involuntary muscle contractions. Better recoveries were associated with lower propofol plasma concentrations. Propofol plasma concentration frequently increased when horses woke from anaesthesia. ConclusionsCaution is warranted when propofol is used for continuous infusion due to variable kinetics, myoclonal activity, poor analgesia, and less desirable recovery quality.

KW - Emulsifiers

KW - Formulations

KW - Horse

KW - Pharmacokinetics

KW - Pharmacolgy

KW - Propofol

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DO - 10.1093/bja/aep377

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JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

SN - 0007-0912

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