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Pharmacokinetics, absolute bioavailability and tolerability of ketamine after intranasal administration to dexmedetomidine sedated dogs

Lise Vlerick (UGent) , Mathias Devreese (UGent) , Kathelijne Peremans (UGent) , Robrecht Dockx (UGent) , Siska Croubels (UGent) , Luc Duchateau (UGent) and Ingeborgh Polis (UGent)
(2020) PLOS ONE. 15(1).
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Abstract
Intranasal ketamine has recently gained interest in human medicine, not only for its sedative, anaesthetic or analgesic properties, but also in the management of treatment resistant depression, where it has been shown to be an effective, fast acting alternative treatment. Since several similarities are reported between human psychiatric disorders and canine anxiety disorders, intranasal ketamine could serve as an alternative treatment for anxiety disordered dogs. However, to the authors knowledge, intranasal administration of ketamine and its pharmacokinetics have never been described in dogs. Therefore, this study aimed to examine the pharmacokinetics, absolute bioavailability and tolerability of intranasal ketamine administration compared with intravenous administration. Seven healthy, adult laboratory Beagle dogs were included in this randomized crossover study. The dogs received 2 mg/kg body weight ketamine intravenously (IV) or intranasally (IN), with a two-week washout period. Prior to ketamine administration, dogs were sedated intramuscularly with dexmedetomidine. Venous blood samples were collected at fixed times until 480 min post-administration and ketamine plasma concentrations were determined by liquid chromatographytandem mass spectrometry. Cardiovascular parameters and sedation scores were recorded at the same time points. Non-compartmental pharmacokinetic analysis revealed a rapid (Tmax = 0.25 +/- 0.14 h) and complete IN bioavailability (F = 147.65 +/- 49.97%). Elimination half-life was similar between both administration routes (T1/2el IV = 1.47 +/- 0.24 h, T1/2el IN = 1.50 +/- 0.97 h). Heart rate and sedation scores were significantly higher at 5 and 10 min following IV administration compared to IN administration, but not at the later time-points.
Keywords
CEREBRAL-BLOOD-FLOW, RANDOMIZED CONTROLLED-TRIAL, 5-HT2A RECEPTOR-BINDING, CONSTANT-RATE-INFUSION, S-KETAMINE, SEPARATION ANXIETY, DRUG-DELIVERY, SEVERE PAIN, NORKETAMINE, MIDAZOLAM

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MLA
Vlerick, Lise, et al. “Pharmacokinetics, Absolute Bioavailability and Tolerability of Ketamine after Intranasal Administration to Dexmedetomidine Sedated Dogs.” PLOS ONE, vol. 15, no. 1, 2020, doi:10.1371/journal.pone.0227762.
APA
Vlerick, L., Devreese, M., Peremans, K., Dockx, R., Croubels, S., Duchateau, L., & Polis, I. (2020). Pharmacokinetics, absolute bioavailability and tolerability of ketamine after intranasal administration to dexmedetomidine sedated dogs. PLOS ONE, 15(1). https://doi.org/10.1371/journal.pone.0227762
Chicago author-date
Vlerick, Lise, Mathias Devreese, Kathelijne Peremans, Robrecht Dockx, Siska Croubels, Luc Duchateau, and Ingeborgh Polis. 2020. “Pharmacokinetics, Absolute Bioavailability and Tolerability of Ketamine after Intranasal Administration to Dexmedetomidine Sedated Dogs.” PLOS ONE 15 (1). https://doi.org/10.1371/journal.pone.0227762.
Chicago author-date (all authors)
Vlerick, Lise, Mathias Devreese, Kathelijne Peremans, Robrecht Dockx, Siska Croubels, Luc Duchateau, and Ingeborgh Polis. 2020. “Pharmacokinetics, Absolute Bioavailability and Tolerability of Ketamine after Intranasal Administration to Dexmedetomidine Sedated Dogs.” PLOS ONE 15 (1). doi:10.1371/journal.pone.0227762.
Vancouver
1.
Vlerick L, Devreese M, Peremans K, Dockx R, Croubels S, Duchateau L, et al. Pharmacokinetics, absolute bioavailability and tolerability of ketamine after intranasal administration to dexmedetomidine sedated dogs. PLOS ONE. 2020;15(1).
IEEE
[1]
L. Vlerick et al., “Pharmacokinetics, absolute bioavailability and tolerability of ketamine after intranasal administration to dexmedetomidine sedated dogs,” PLOS ONE, vol. 15, no. 1, 2020.
@article{8644255,
  abstract     = {{Intranasal ketamine has recently gained interest in human medicine, not only for its sedative, anaesthetic or analgesic properties, but also in the management of treatment resistant depression, where it has been shown to be an effective, fast acting alternative treatment. Since several similarities are reported between human psychiatric disorders and canine anxiety disorders, intranasal ketamine could serve as an alternative treatment for anxiety disordered dogs. However, to the authors knowledge, intranasal administration of ketamine and its pharmacokinetics have never been described in dogs. Therefore, this study aimed to examine the pharmacokinetics, absolute bioavailability and tolerability of intranasal ketamine administration compared with intravenous administration. Seven healthy, adult laboratory Beagle dogs were included in this randomized crossover study. The dogs received 2 mg/kg body weight ketamine intravenously (IV) or intranasally (IN), with a two-week washout period. Prior to ketamine administration, dogs were sedated intramuscularly with dexmedetomidine. Venous blood samples were collected at fixed times until 480 min post-administration and ketamine plasma concentrations were determined by liquid chromatographytandem mass spectrometry. Cardiovascular parameters and sedation scores were recorded at the same time points. Non-compartmental pharmacokinetic analysis revealed a rapid (Tmax = 0.25 +/- 0.14 h) and complete IN bioavailability (F = 147.65 +/- 49.97%). Elimination half-life was similar between both administration routes (T1/2el IV = 1.47 +/- 0.24 h, T1/2el IN = 1.50 +/- 0.97 h). Heart rate and sedation scores were significantly higher at 5 and 10 min following IV administration compared to IN administration, but not at the later time-points.}},
  articleno    = {{e0227762}},
  author       = {{Vlerick, Lise and Devreese, Mathias and Peremans, Kathelijne and Dockx, Robrecht and Croubels, Siska and Duchateau, Luc and Polis, Ingeborgh}},
  issn         = {{1932-6203}},
  journal      = {{PLOS ONE}},
  keywords     = {{CEREBRAL-BLOOD-FLOW,RANDOMIZED CONTROLLED-TRIAL,5-HT2A RECEPTOR-BINDING,CONSTANT-RATE-INFUSION,S-KETAMINE,SEPARATION ANXIETY,DRUG-DELIVERY,SEVERE PAIN,NORKETAMINE,MIDAZOLAM}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{13}},
  title        = {{Pharmacokinetics, absolute bioavailability and tolerability of ketamine after intranasal administration to dexmedetomidine sedated dogs}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0227762}},
  volume       = {{15}},
  year         = {{2020}},
}

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