Pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular administration in male cats

Bruno H Pypendop, Juhana Honkavaara, Jan Ilkiw

Research output: Contribution to journalArticle

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Abstract

Objective To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats. Study design Prospective randomized crossover experimental study. Animals A total of eight healthy adult male castrated cats aged 1–2 years. Methods Cats were administered dexmedetomidine (25 μg kg–1) IM (treatment D25IM) or intravenously (IV; treatment D25IV); MK-467 (600 μg kg–1) IM (treatment MK600IM) or IV (treatment MK600IV); or dexmedetomidine (25 μg kg–1) IM with 300, 600 or 1200 μg kg–1 MK-467 IM (treatments D25MK300IM, D25MK600IM and D25MK1200IM). D25MK600IM was the only combination treatment analyzed. Blood samples were obtained prior to drug administration and at various times for 5 hours (D25IV) or 8 hours (all other treatments) thereafter. Plasma dexmedetomidine and MK-467 concentrations were measured using liquid chromatography/mass spectrometry. Compartment models were fitted to the time–concentration data. Results A one-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IM, and the time–plasma MK-467 concentration data in cats administered MK600IM and D25MK600IM. A two-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IV and D25MK600IM, and the time–plasma MK-467 concentration data in cats administered MK600IV. Median (range) area under the time–concentration curve, absorption rate half-life, maximum concentration, time to maximum concentration and terminal half-life for dexmedetomidine in D25IM and D25MK600IM were 1129 (792–1890) and 924 (596–1649) ng minute mL–1, 4.4 (0.4–15.7) and 2.3 (0.2–8.0) minutes, 10.2 (4.8–16.9) and 17.8 (15.8–73.5) ng mL–1, 17.8 (2.6–44.9) and 5.2 (1.2–15.1) minutes and 62 (52–139) and 50 (31–125) minutes, respectively. Rate of absorption but not systemic exposure was significantly influenced by treatment. No significant differences were observed in MK-467 pharmacokinetic parameters in MK600IM and D25MK600IM. Conclusions and clinical relevance MK-467 significantly influenced the disposition of dexmedetomidine, whereas dexmedetomidine did not significantly affect the disposition of MK-467 when the drugs were coadministered IM.

Original languageEnglish (US)
Pages (from-to)823-831
Number of pages9
JournalVeterinary Anaesthesia and Analgesia
Volume44
Issue number4
DOIs
StatePublished - Jul 1 2017

Fingerprint

L 659066
dexmedetomidine
Dexmedetomidine
intramuscular injection
pharmacokinetics
Cats
Pharmacokinetics
cats
half life
Half-Life
Therapeutics
drugs
Liquid Chromatography
Pharmaceutical Preparations
Cross-Over Studies
liquid chromatography
Area Under Curve

Keywords

  • antagonist
  • cat
  • dexmedetomidine

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular administration in male cats. / Pypendop, Bruno H; Honkavaara, Juhana; Ilkiw, Jan.

In: Veterinary Anaesthesia and Analgesia, Vol. 44, No. 4, 01.07.2017, p. 823-831.

Research output: Contribution to journalArticle

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title = "Pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular administration in male cats",
abstract = "Objective To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats. Study design Prospective randomized crossover experimental study. Animals A total of eight healthy adult male castrated cats aged 1–2 years. Methods Cats were administered dexmedetomidine (25 μg kg–1) IM (treatment D25IM) or intravenously (IV; treatment D25IV); MK-467 (600 μg kg–1) IM (treatment MK600IM) or IV (treatment MK600IV); or dexmedetomidine (25 μg kg–1) IM with 300, 600 or 1200 μg kg–1 MK-467 IM (treatments D25MK300IM, D25MK600IM and D25MK1200IM). D25MK600IM was the only combination treatment analyzed. Blood samples were obtained prior to drug administration and at various times for 5 hours (D25IV) or 8 hours (all other treatments) thereafter. Plasma dexmedetomidine and MK-467 concentrations were measured using liquid chromatography/mass spectrometry. Compartment models were fitted to the time–concentration data. Results A one-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IM, and the time–plasma MK-467 concentration data in cats administered MK600IM and D25MK600IM. A two-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IV and D25MK600IM, and the time–plasma MK-467 concentration data in cats administered MK600IV. Median (range) area under the time–concentration curve, absorption rate half-life, maximum concentration, time to maximum concentration and terminal half-life for dexmedetomidine in D25IM and D25MK600IM were 1129 (792–1890) and 924 (596–1649) ng minute mL–1, 4.4 (0.4–15.7) and 2.3 (0.2–8.0) minutes, 10.2 (4.8–16.9) and 17.8 (15.8–73.5) ng mL–1, 17.8 (2.6–44.9) and 5.2 (1.2–15.1) minutes and 62 (52–139) and 50 (31–125) minutes, respectively. Rate of absorption but not systemic exposure was significantly influenced by treatment. No significant differences were observed in MK-467 pharmacokinetic parameters in MK600IM and D25MK600IM. Conclusions and clinical relevance MK-467 significantly influenced the disposition of dexmedetomidine, whereas dexmedetomidine did not significantly affect the disposition of MK-467 when the drugs were coadministered IM.",
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T1 - Pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular administration in male cats

AU - Pypendop, Bruno H

AU - Honkavaara, Juhana

AU - Ilkiw, Jan

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Objective To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats. Study design Prospective randomized crossover experimental study. Animals A total of eight healthy adult male castrated cats aged 1–2 years. Methods Cats were administered dexmedetomidine (25 μg kg–1) IM (treatment D25IM) or intravenously (IV; treatment D25IV); MK-467 (600 μg kg–1) IM (treatment MK600IM) or IV (treatment MK600IV); or dexmedetomidine (25 μg kg–1) IM with 300, 600 or 1200 μg kg–1 MK-467 IM (treatments D25MK300IM, D25MK600IM and D25MK1200IM). D25MK600IM was the only combination treatment analyzed. Blood samples were obtained prior to drug administration and at various times for 5 hours (D25IV) or 8 hours (all other treatments) thereafter. Plasma dexmedetomidine and MK-467 concentrations were measured using liquid chromatography/mass spectrometry. Compartment models were fitted to the time–concentration data. Results A one-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IM, and the time–plasma MK-467 concentration data in cats administered MK600IM and D25MK600IM. A two-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IV and D25MK600IM, and the time–plasma MK-467 concentration data in cats administered MK600IV. Median (range) area under the time–concentration curve, absorption rate half-life, maximum concentration, time to maximum concentration and terminal half-life for dexmedetomidine in D25IM and D25MK600IM were 1129 (792–1890) and 924 (596–1649) ng minute mL–1, 4.4 (0.4–15.7) and 2.3 (0.2–8.0) minutes, 10.2 (4.8–16.9) and 17.8 (15.8–73.5) ng mL–1, 17.8 (2.6–44.9) and 5.2 (1.2–15.1) minutes and 62 (52–139) and 50 (31–125) minutes, respectively. Rate of absorption but not systemic exposure was significantly influenced by treatment. No significant differences were observed in MK-467 pharmacokinetic parameters in MK600IM and D25MK600IM. Conclusions and clinical relevance MK-467 significantly influenced the disposition of dexmedetomidine, whereas dexmedetomidine did not significantly affect the disposition of MK-467 when the drugs were coadministered IM.

AB - Objective To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats. Study design Prospective randomized crossover experimental study. Animals A total of eight healthy adult male castrated cats aged 1–2 years. Methods Cats were administered dexmedetomidine (25 μg kg–1) IM (treatment D25IM) or intravenously (IV; treatment D25IV); MK-467 (600 μg kg–1) IM (treatment MK600IM) or IV (treatment MK600IV); or dexmedetomidine (25 μg kg–1) IM with 300, 600 or 1200 μg kg–1 MK-467 IM (treatments D25MK300IM, D25MK600IM and D25MK1200IM). D25MK600IM was the only combination treatment analyzed. Blood samples were obtained prior to drug administration and at various times for 5 hours (D25IV) or 8 hours (all other treatments) thereafter. Plasma dexmedetomidine and MK-467 concentrations were measured using liquid chromatography/mass spectrometry. Compartment models were fitted to the time–concentration data. Results A one-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IM, and the time–plasma MK-467 concentration data in cats administered MK600IM and D25MK600IM. A two-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IV and D25MK600IM, and the time–plasma MK-467 concentration data in cats administered MK600IV. Median (range) area under the time–concentration curve, absorption rate half-life, maximum concentration, time to maximum concentration and terminal half-life for dexmedetomidine in D25IM and D25MK600IM were 1129 (792–1890) and 924 (596–1649) ng minute mL–1, 4.4 (0.4–15.7) and 2.3 (0.2–8.0) minutes, 10.2 (4.8–16.9) and 17.8 (15.8–73.5) ng mL–1, 17.8 (2.6–44.9) and 5.2 (1.2–15.1) minutes and 62 (52–139) and 50 (31–125) minutes, respectively. Rate of absorption but not systemic exposure was significantly influenced by treatment. No significant differences were observed in MK-467 pharmacokinetic parameters in MK600IM and D25MK600IM. Conclusions and clinical relevance MK-467 significantly influenced the disposition of dexmedetomidine, whereas dexmedetomidine did not significantly affect the disposition of MK-467 when the drugs were coadministered IM.

KW - antagonist

KW - cat

KW - dexmedetomidine

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