Pharmacokinetics of dexmedetomidine, <scp>MK</scp>‐467, and their combination following intravenous administration in male cats

Pypendop, Bruno H.; Honkavaara, Juhana; Ilkiw, Jan E.

doi:10.1111/jvp.12302

Cited by 18 publications

(6 citation statements)

References 20 publications

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“…Vatinoxan increases the volume of distribution of dexmedetomidine in dogs and cats after IV co-administration (Honkavaara et al 2012;Pypendop et al 2016). The tissue concentrations in the current study represent only one time point and it is unknown if the concentrations subsequently increased or decreased.…”

Section: Discussionmentioning

confidence: 81%

“…In brief, vatinoxan has been shown to either attenuate or prevent the cardiovascular effects of various α 2 -adrenoceptor agonists in dogs (Pagel et al 1998;Enouri et al 2008;Honkavaara et al 2008Honkavaara et al , 2011Rolfe et al 2012), horses (Bryant et al 1998;de Vries et al 2016;Tapio et al 2018), sheep (Bryant et al 1998;Raekallio et al 2010: Adam et al 2018) and cats (Pypendop et al 2017a;Siao et al 2017). Moreover, its impact on agonistinduced sedation appears to be minor and more related to alteration on the disposition of coadministered agonists drugs through attenuation of their cardiovascular effects (Vainionpaa et al 2013;Bennett et al 2016;Restitutti et al 2017;Adam et al 2018;Pypendop et al 2016Pypendop et al , 2017bHonkavaara et al 2017a, b). However, to date, direct evidence of the inability of vatinoxan to cross the mammalian blood-brain barrier in vivo only exists for rats and marmosets (Clineschmidt et al 1988).…”

Section: Introductionmentioning

confidence: 99%

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Concentrations of medetomidine enantiomers and vatinoxan, an α2-adrenoceptor antagonist, in plasma and central nervous tissue after intravenous coadministration in dogs

Honkavaara

Raekallio

Syrja

et al. 2020

Veterinary Anaesthesia and Analgesia

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Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Concentrations of medetomidine enantiomers and vatinoxan, an α2-adrenoceptor antagonist, in plasma and central nervous tissue after intravenous coadministration in dogs

Honkavaara

Raekallio

Syrja

et al. 2020

Veterinary Anaesthesia and Analgesia

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“…3,4 The most well-known side effects of dexmedetomidine are centered around its cardiovascular effects that lead to peripheral vasoconstriction, bradycardia and decreased cardiac output. [5][6][7] Dexmedetomidine also has effects on the endocrine system and glucose homeostasis. [8][9][10][11][12][13][14][15] Alpha(α)2-adrenoceptors are associated with modulation of the sympathoadrenal system.…”

Section: Introductionmentioning

confidence: 99%

Effects of dexmedetomidine on glucose homeostasis in healthy cats

Bouillon

Duke

Focken

et al. 2019

Journal of Feline Medicine and Surgery

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Objectives Alpha(α)2-agonist administration has been documented to increase blood glucose concentrations in many species. The aim of this study was to further describe the effect of dexmedetomidine on glucose and its regulatory hormones in healthy cats. Methods A randomized crossover study using eight healthy cats with a 14 day washout period was used to assess the effect of dexmedetomidine (10 μg/kg IV) and saline on glucose, cortisol, insulin, glucagon and non-esterified fatty acid (NEFA) concentrations at 0, 20, 60, 120 and 180 mins post-administration. Glucose:insulin ratios were calculated for each time point. Results Within the dexmedetomidine group, significant differences ( P <0.05) were detected: increased median (range) blood glucose concentrations at 60 mins (11.55 mmol/l [5.9–16.6 mmol/l]) and 120 mins (12.0 mmol/l [6.1–13.8 mmol/l]) compared with baseline (6.05 mmol/l [4.8–13.3 mmol/l]); decreased glucagon concentrations at 120 mins (3.8 pmol/l [2.7–8.8 pmol/l]) and 180 mins (4.7 pmol/l [2.1–8.2 pmol/l]) compared with baseline (11.85 pmol/l [8.3–17.2 pmol/l]); decreased NEFA concentrations at 60 mins (0.281 mmol/l [0.041–1.357 mmol/l]) and 120 mins (0.415 mmol/l [0.035–1.356 mmol/l]) compared with baseline (0.937 mmol/l [0.677–1.482 mmol/l]); and significantly larger ( P <0.05) glucose:insulin ratios at 60 mins compared with baseline. Insulin and cortisol concentrations were not significantly changed after dexmedetomidine administration. Conclusions and relevance Feline practitioners should be aware of the endocrine effects associated with the use of α2-agonists, particularly when interpreting blood glucose concentrations. The transient effects of dexmedetomidine on glucose homeostasis are unlikely to significantly affect clinical practice.

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“…MK-467 markedly influence the early disposition of dexmedetomidine without obvious effects on the plasma concentrations of the later in dogs, cats as well as sheep, whereas dexmedetomidine does affects the disposition of MK-467, but only minimally (Honkavaara et al, 2011;Pypendop et al, 2016;Adam et al, 2018). It has been analyzed that MK-467 elevates the early stage plasma concentration of both medetomidine and butorphanol when administrated IM in the same syringe and thereby results in deeper initial sedation for a shorter duration (Kallio-Kujala et al, 2018a;Restitutti et al, 2017).…”

Section: Pharmacokinetic Effectsmentioning

confidence: 99%

Various Systemic Effects of MK-467, A Peripherally Acting α2-adrenoceptor Antagonist in Different Animal Species: An Overview

Akash

Hoque

Amarpal

2020

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Most commonly used α2-adrenoceptor agonist shows adverse cardiovascular effects during anaesthesia. They mainly depress the cardiovascular system by provoking vasoconstriction followed by bradycardia. Although α2-adrenoceptor antagonist like atipamezole can reverse these effects along with that they also reverse the sedation and nociception. Concomitant administration of peripherally acting α2-adrenoceptor antagonist MK-467 can reverse the adverse cardiovascular effect of α2-adrenoceptor agonists without affecting the sedation and nociception. MK-467 has been successfully used in different animals like dogs, cats, sheep, horses along with different α2-adrenoceptor agonist drugs. This review aims to summarize the effects of MK-467 on sedation, cardiopulmonary system, the minimum alveolar concentration of different inhalant anaesthetics, plasma drug concentration, plasma glucose and insulin in different animals.

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Pharmacokinetics of dexmedetomidine, MK‐467, and their combination following intravenous administration in male cats

Abstract: This study characterized the pharmacokinetics of dexmedetomidine, MK-467, and their combination following intravenous bolus administration to cats. Seven 6 to 7 year old male neutered cats, weighting 5.1 ± 0.7 kg were used in a randomized, cross-over design. Dexmedetomidine [12.5 (D12.5)

Cited by 18 publications

References 20 publications

Concentrations of medetomidine enantiomers and vatinoxan, an α2-adrenoceptor antagonist, in plasma and central nervous tissue after intravenous coadministration in dogs

Concentrations of medetomidine enantiomers and vatinoxan, an α2-adrenoceptor antagonist, in plasma and central nervous tissue after intravenous coadministration in dogs

Effects of dexmedetomidine on glucose homeostasis in healthy cats

Various Systemic Effects of MK-467, A Peripherally Acting α2-adrenoceptor Antagonist in Different Animal Species: An Overview

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