Pharmacokinetics of morphine in combination with dexmedetomidine and maropitant following intramuscular injection in dogs anaesthetized with halothane

J Vet Pharmacol Ther. 2020 Mar;43(2):153-161. doi: 10.1111/jvp.12831. Epub 2019 Dec 19.

Abstract

The purpose of this study was to evaluate the pharmacokinetics of morphine in combination with dexmedetomidine and maropitant injected intramuscularly in dogs under general anaesthesia. Eight healthy dogs weighing 25.76 ± 3.16 kg and 3.87 ± 1.64 years of age were used in a crossover study. Dogs were randomly allocated to four groups: (1) morphine 0.6 mg/kg; (2) morphine 0.3 mg/kg + dexmedetomidine 5 μg/kg; (3) morphine 0.3 mg/kg + maropitant 1 mg/kg; (4) morphine 0.2 mg/kg + dexmedetomidine 3 μg/kg + maropitant 0.7 mg/kg. Blood samples were collected before, 15 and 30 min, and 1, 2, 3 4, 6 and 8 hr after injection of the test drugs. Plasma concentration of the drugs was determined by liquid chromatography-mass spectrometry. The elimination half-life (T1/2 ) of morphine was higher and the clearance rate (CL) was lower when combined with dexmedetomidine (T1/2 = 77.72 ± 20.27 min, CL = 119.41 ± 23.34 ml kg-1 min-1 ) compared to maropitant (T1/2 = 52.73 min ± 13.823 ml kg-1 min-1 , CL = 178.57 ± 70.55) or morphine alone at higher doses (T1/2 = 50.53 ± 12.55 min, CL = 187.24 ± 34.45 ml kg-1 min-1 ). Combining morphine with dexmedetomidine may increase the dosing interval of morphine and may have a clinical advantage.

Keywords: alpha-2-adrenoceptor agonist; dogs; halothane; intramuscular; neurokinin-1 receptor antagonist; opioid.

Publication types

  • Randomized Controlled Trial, Veterinary

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / blood
  • Analgesics, Opioid / pharmacokinetics
  • Anesthetics, Inhalation / pharmacology
  • Animals
  • Antiemetics / administration & dosage
  • Antiemetics / blood
  • Antiemetics / pharmacokinetics
  • Area Under Curve
  • Cross-Over Studies
  • Dexmedetomidine / administration & dosage
  • Dexmedetomidine / pharmacokinetics*
  • Dogs / blood*
  • Drug Therapy, Combination
  • Half-Life
  • Halothane / pharmacology*
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / blood
  • Hypnotics and Sedatives / pharmacokinetics
  • Injections, Intramuscular
  • Morphine / administration & dosage
  • Morphine / pharmacokinetics*
  • Quinuclidines / administration & dosage
  • Quinuclidines / pharmacokinetics*

Substances

  • Analgesics, Opioid
  • Anesthetics, Inhalation
  • Antiemetics
  • Hypnotics and Sedatives
  • Quinuclidines
  • maropitant
  • Dexmedetomidine
  • Morphine
  • Halothane