title: Effects of acepromazine or dexmedetomidine on fentanyl disposition in dogs during recovery from isoflurane anesthesia.
abstract: OBJECTIVE
  To describe fentanyl pharmacokinetics during isoflurane anesthesia and on recovery from anesthesia with concurrent administration of acepromazine, dexmedetomidine or saline in dogs.
  
  
  METHODS
  Experimental blinded, randomized, crossover study.
  
  
  METHODS
  Seven adult hound dogs.
  
  
  METHODS
  Dogs were administered intravenous (IV) fentanyl as a bolus (5 μg kg(-1)) followed by an infusion (5 μg kg(-1) hour(-1)) for 120 minutes during isoflurane anesthesia and emergence from anesthesia, and for 60 minutes after extubation during recovery from anesthesia. At the time of extubation, dexmedetomidine (2.5 μg kg(-1)), acepromazine (0.05 mg kg(-1)) or saline were administered IV. Venous blood was sampled during the maintenance and recovery periods. Fentanyl plasma concentrations were measured using high-performance liquid chromatography-mass spectrometry and population pharmacokinetic analyses were performed.
  
  
  RESULTS
  Mean fentanyl plasma concentrations were 1.6-4.5 ng mL(-1) during isoflurane anesthesia and 1.6-2.0 ng mL(-1) during recovery from anesthesia. Recovery from isoflurane anesthesia without sedation was associated with an increase in the volume of the central compartment from 0.80 to 1.02 L kg(-1). After administration of acepromazine, systemic clearance of fentanyl increased from 31.5 to 40.3 mL minute(-1) kg(-1) and the volume of the central compartment increased from 0.70 to 0.94 L kg(-1). Administration of dexmedetomidine did not significantly change fentanyl pharmacokinetics. Inter-individual variability for fentanyl parameter estimates in all treatments ranged from 2.2% to 54.5%, and residual error ranged from 6.3% to 13.4%.
  
  
  CONCLUSIONS
  The dose rates of fentanyl used in this study achieved previously established analgesic plasma concentrations for the duration of the infusion. Despite alterations in fentanyl pharmacokinetics, differences in fentanyl plasma concentrations among treatments during recovery from anesthesia were small and were unlikely to be of clinical significance.
authors.affiliation: Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Keating
authors.affiliation: Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Kerr
authors.affiliation: Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
authors.forename: Wayne
authors.initials: W
authors.lastname: McDonell
authors.affiliation: Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Valverde
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
authors.forename: Ron
authors.initials: R
authors.lastname: Johnson
authors.affiliation: Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Knych
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Edginton
mesh_terms: D000075:Acepromazine / Q000008:administration & dosage / Q000494:pharmacology; D000762:Anesthesia Recovery Period; D000769:Anesthesia, Inhalation / Q000662:veterinary; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D018592:Cross-Over Studies; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs / Q000502:physiology* / Q000601:surgery; D004311:Double-Blind Method; D005283:Fentanyl / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D000075:Acepromazine; D020927:Dexmedetomidine; D007530:Isoflurane; D005283:Fentanyl
keywords: acepromazine; anesthesia; dexmedetomidine; dog; fentanyl; recovery