Pharmacokinetics of dexmedetomidine during administration of vatinoxan in male neutered cats anesthetized with isoflurane

Bruno H Pypendop, Hanna Ahokoivu, Juhana Honkavaara

Research output: Contribution to journalArticle

Abstract

Dexmedetomidine is an alpha-2 adrenoceptor agonist, and vatinoxan is an alpha-2 antagonist believed to poorly cross the blood–brain barrier in cats. Dexmedetomidine–vatinoxan combinations are of interest in anesthetized cats because the anesthetic sparing effect of dexmedetomidine may be preserved while vatinoxan attenuates the adverse cardiovascular effects of dexmedetomidine. The aim of this study was to characterize the pharmacokinetics of dexmedetomidine in cats during administration of isoflurane and vatinoxan. Six healthy adult male castrated cats were anesthetized with isoflurane in oxygen. Vatinoxan was administered using a target-controlled infusion system intended to maintain a plasma concentration of 4 µg/ml. Dexmedetomidine, 35 µg/kg was administered intravenously over 5 min. Plasma dexmedetomidine and vatinoxan concentrations were measured at selected time points ranging from prior to 8 hr after dexmedetomidine administration using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-concentration data using nonlinear mixed-effect modeling. A three-compartment model best fitted the data. Typical value (% interindividual variability) for the three-compartment volumes (ml/kg), the metabolic clearance and the two intercompartment distribution clearances (ml min−1kg−1) were 168 (259), 318 (35), 1,425 (18), 12.4 (31), 39.1 (18), and 29.6 (17), respectively. Mean ± standard deviation plasma vatinoxan concentration was 2.6 ± 0.6 µg/ml.

Original languageEnglish (US)
JournalJournal of Veterinary Pharmacology and Therapeutics
DOIs
StateAccepted/In press - Jan 1 2019

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dexmedetomidine
Dexmedetomidine
Isoflurane
isoflurane
pharmacokinetics
Cats
Pharmacokinetics
cats
blood-brain barrier
Tandem Mass Spectrometry
Liquid Chromatography
anesthetics
Adrenergic Receptors
liquid chromatography
agonists
Anesthetics
antagonists
Oxygen
oxygen

Keywords

  • cats
  • isoflurane
  • receptors adrenergic alpha-2

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

Cite this

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title = "Pharmacokinetics of dexmedetomidine during administration of vatinoxan in male neutered cats anesthetized with isoflurane",
abstract = "Dexmedetomidine is an alpha-2 adrenoceptor agonist, and vatinoxan is an alpha-2 antagonist believed to poorly cross the blood–brain barrier in cats. Dexmedetomidine–vatinoxan combinations are of interest in anesthetized cats because the anesthetic sparing effect of dexmedetomidine may be preserved while vatinoxan attenuates the adverse cardiovascular effects of dexmedetomidine. The aim of this study was to characterize the pharmacokinetics of dexmedetomidine in cats during administration of isoflurane and vatinoxan. Six healthy adult male castrated cats were anesthetized with isoflurane in oxygen. Vatinoxan was administered using a target-controlled infusion system intended to maintain a plasma concentration of 4 µg/ml. Dexmedetomidine, 35 µg/kg was administered intravenously over 5 min. Plasma dexmedetomidine and vatinoxan concentrations were measured at selected time points ranging from prior to 8 hr after dexmedetomidine administration using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-concentration data using nonlinear mixed-effect modeling. A three-compartment model best fitted the data. Typical value ({\%} interindividual variability) for the three-compartment volumes (ml/kg), the metabolic clearance and the two intercompartment distribution clearances (ml min−1kg−1) were 168 (259), 318 (35), 1,425 (18), 12.4 (31), 39.1 (18), and 29.6 (17), respectively. Mean ± standard deviation plasma vatinoxan concentration was 2.6 ± 0.6 µg/ml.",
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author = "Pypendop, {Bruno H} and Hanna Ahokoivu and Juhana Honkavaara",
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T1 - Pharmacokinetics of dexmedetomidine during administration of vatinoxan in male neutered cats anesthetized with isoflurane

AU - Pypendop, Bruno H

AU - Ahokoivu, Hanna

AU - Honkavaara, Juhana

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Dexmedetomidine is an alpha-2 adrenoceptor agonist, and vatinoxan is an alpha-2 antagonist believed to poorly cross the blood–brain barrier in cats. Dexmedetomidine–vatinoxan combinations are of interest in anesthetized cats because the anesthetic sparing effect of dexmedetomidine may be preserved while vatinoxan attenuates the adverse cardiovascular effects of dexmedetomidine. The aim of this study was to characterize the pharmacokinetics of dexmedetomidine in cats during administration of isoflurane and vatinoxan. Six healthy adult male castrated cats were anesthetized with isoflurane in oxygen. Vatinoxan was administered using a target-controlled infusion system intended to maintain a plasma concentration of 4 µg/ml. Dexmedetomidine, 35 µg/kg was administered intravenously over 5 min. Plasma dexmedetomidine and vatinoxan concentrations were measured at selected time points ranging from prior to 8 hr after dexmedetomidine administration using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-concentration data using nonlinear mixed-effect modeling. A three-compartment model best fitted the data. Typical value (% interindividual variability) for the three-compartment volumes (ml/kg), the metabolic clearance and the two intercompartment distribution clearances (ml min−1kg−1) were 168 (259), 318 (35), 1,425 (18), 12.4 (31), 39.1 (18), and 29.6 (17), respectively. Mean ± standard deviation plasma vatinoxan concentration was 2.6 ± 0.6 µg/ml.

AB - Dexmedetomidine is an alpha-2 adrenoceptor agonist, and vatinoxan is an alpha-2 antagonist believed to poorly cross the blood–brain barrier in cats. Dexmedetomidine–vatinoxan combinations are of interest in anesthetized cats because the anesthetic sparing effect of dexmedetomidine may be preserved while vatinoxan attenuates the adverse cardiovascular effects of dexmedetomidine. The aim of this study was to characterize the pharmacokinetics of dexmedetomidine in cats during administration of isoflurane and vatinoxan. Six healthy adult male castrated cats were anesthetized with isoflurane in oxygen. Vatinoxan was administered using a target-controlled infusion system intended to maintain a plasma concentration of 4 µg/ml. Dexmedetomidine, 35 µg/kg was administered intravenously over 5 min. Plasma dexmedetomidine and vatinoxan concentrations were measured at selected time points ranging from prior to 8 hr after dexmedetomidine administration using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-concentration data using nonlinear mixed-effect modeling. A three-compartment model best fitted the data. Typical value (% interindividual variability) for the three-compartment volumes (ml/kg), the metabolic clearance and the two intercompartment distribution clearances (ml min−1kg−1) were 168 (259), 318 (35), 1,425 (18), 12.4 (31), 39.1 (18), and 29.6 (17), respectively. Mean ± standard deviation plasma vatinoxan concentration was 2.6 ± 0.6 µg/ml.

KW - cats

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