Clinical and pharmacokinetic interactions between oral fluconazole and intravenous ketamine and midazolam in dogs

Berke, Kara; KuKanich, Butch; Orchard, Ron; Rankin, David C.; Joo, Hyun

doi:10.1016/j.vaa.2019.06.007

Cited by 4 publications

(5 citation statements)

References 15 publications

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“…Furthermore, the individual examination of each enantiomer in this study complicates direct comparison with existing pharmacokinetic models for racemic ketamine. Notably, the observed plasma concentrations for both racemic ketamine and norketamine align closely with the anticipated values derived from previously published pharmacokinetic parameters [21][22][23][26][27][28][29][30]. These observations imply that the pharmacokinetics of ketamine may not be significantly impacted by the simultaneous administration of common anaesthetic drugs, as has been observed with Figure 6.…”

Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 85%

“…The majority of pharmacokinetic investigations concerning ketamine in dogs have utilized significantly higher doses and, in many instances, have involved concomitant administration of other anaesthetic agents, consequently influencing its pharmacokinetic profile [21][22][23][24][25][26][27][28][29][30]. Nevertheless, when applying the reported kinetic variable to low-dose administration regimens in simulation analysis, it becomes evident that the estimated concentrations in dogs are consistently three to five times lower than those observed in humans [18,31].…”

Section: Et Al Reported Ketamine's Analgesic Activity Even Atmentioning

confidence: 99%

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Stereoselective Pharmacokinetics of Ketamine Administered at a Low Dose in Awake Dogs

Pargätzi,

Bergadano,

Spadavecchia

et al. 2024

Animals

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The present study aimed to examine the stereoselective pharmacokinetics of racemic ketamine in dogs at low doses. The secondary aims were to identify associated behavioural effects and propose a ketamine infusion rate. The study was conducted on nine intact male beagles, with each dog undergoing two treatments (BOL and INF). For treatment BOL, an intravenous bolus of 1 mg/kg was administered over 2 min. The treatment INF involved an initial bolus of 0.5 mg/kg given over 1 min, followed by an infusion at 0.01 mg/kg/min for 1 h. Blood samples were collected for pharmacokinetic analysis. The median R/S enantiomer ratio of ketamine remained close to 1 throughout the study. Levels of S-norketamine were significantly higher than those of R-norketamine across all time points. Based on the collected data, the infusion rate predicted to achieve a steady-state racemic ketamine plasma concentration of 150 ng/mL was 0.028 mg/kg/min. Higher scores for behavioural effects were observed within the first five minutes following bolus administration. The most common behaviours observed were disorientation, head movements and staring eyes. Furthermore, employing ROC curve analysis, a racemic ketamine plasma concentration of 102 ng/mL was defined as the cut-off value, correlating with the occurrence of undesirable behavioural patterns.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 85%

Section: Et Al Reported Ketamine's Analgesic Activity Even Atmentioning

confidence: 99%

See 1 more Smart Citation

Stereoselective Pharmacokinetics of Ketamine Administered at a Low Dose in Awake Dogs

Pargätzi,

Bergadano,

Spadavecchia

et al. 2024

Animals

View full text Add to dashboard Cite

show abstract

“…Furthermore, the individual examination of each enantiomer in this study complicates direct comparison with existing pharmacokinetic models for total ketamine. Notably, the observed plasma concentrations for both total ketamine and norketamine align closely with the anticipated values derived from previously published pharmacokinetic parameters [21][22][23][26][27][28][29][30]. These observations imply that the pharmacokinetics of ketamine may not be significantly impacted by the simultaneous administration of common anesthetic drugs, as has been observed with fluconazole, for example, which, although reported, was not deemed clinically significant in the context of anaesthesia [29].…”

Section: Discussionsupporting

confidence: 85%

“…The majority of pharmacokinetic investigations concerning ketamine in dogs have utilized significantly higher doses and, in many instances, have involved concomitant administration of other anaesthetic agents, consequently influencing its pharmacokinetic profile [21][22][23][24][25][26][27][28][29][30]. When extrapolating the simulated blood concentration from these studies to low doses, it becomes evident that the concentrations in dogs are consistently 3 to 5 times lower than those observed in humans [18,31].…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Pharmacokinetics of Ketamine Administered at Low Dose in Awake Dogs

Pargätzi,

Bergadano,

Spadavecchia

et al. 2023

Preprint

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The present study aimed to examine the stereoselective pharmacokinetics of racemic ketamine in dogs at low dose. Secondary aims were to identify associated behavioural side effects and propose a ketamine infusion rate. The study was conducted on nine intact male beagles, with each dog undergoing two treatments (BOL and INF). For treatment BOL, a single intravenous bolus of 1 mg/kg racemic ketamine was administered over 2 minutes. The treatment INF involved an initial bolus of 0.5 mg/kg given over 1 minute, followed by an infusion at 0.01 mg/kg/min for 1 hour. Blood samples were collected from the left cephalic vein for pharmacokinetic analysis. The median R/S enantiomer ratio of ketamine remained close to 1 throughout the study. However, levels of S-norketamine were significantly higher than those of R-norketamine across all time points. Based on the collected data, the infusion rate predicted to achieve a steady state racemic ketamine plasma concentration of 150 ng/mL was 1.7 mg/kg/h. Furthermore, employing ROC curve analysis, a racemic ketamine plasma concentration of 102 ng/mL was defined as the cut-off value, correlating with the occurrence of undesirable behavioural patterns.

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Centrally Acting Muscle Relaxants

Hay Kraus

2024

Pharmacology in Veterinary Anesthesia and Analgesia

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Clinical and pharmacokinetic interactions between oral fluconazole and intravenous ketamine and midazolam in dogs

Cited by 4 publications

References 15 publications

Stereoselective Pharmacokinetics of Ketamine Administered at a Low Dose in Awake Dogs

Stereoselective Pharmacokinetics of Ketamine Administered at a Low Dose in Awake Dogs

Stereoselective Pharmacokinetics of Ketamine Administered at Low Dose in Awake Dogs

Centrally Acting Muscle Relaxants

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