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

Autoři: Lise Vlerick aff001;  Mathias Devreese aff002;  Kathelijne Peremans aff003;  Robrecht Dockx aff003;  Siska Croubels aff002;  Luc Duchateau aff005;  Ingeborgh Polis aff001
Působiště autorů: Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium aff001;  Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium aff002;  Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium aff003;  Department of Psychiatry and Medical Psychology, Ghent Experimental Psychiatry (GHEP) lab, Ghent University, Ghent, Belgium aff004;  Biometrics Research Centre, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227762


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 wash-out 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 chromatography-tandem 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.

Klíčová slova:

Dogs – Drug administration – Heart rate – Pharmacokinetics – Routes of administration – Sedation – Sedatives – Intranasal administration


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