Pharmacokinetics of Ketamine and Norketamine After Oral Administration of a Liquid Formulation of Ketamine

Kubota,

doi:10.4021/jcs196e

Cited by 4 publications

(5 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The bioavailability of oral ketamine is approximately 20% to 30% [ 26 , 27 ], time to peak in plasma and its onset of analgesic action is 30 minutes, while the sedative activity depends on the administered dose. The half-life of ketamine is short and higher than the half-life of other sedative or analgesic drugs such as nitrous oxide, propofol, and fentanyl [ 23 , 28 , 29 ]. In comparison to IV administration, orally administered ketamine has fewer adverse effects, and no serious drug interaction has been reported [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of low dose oral ketamine for controlling pain and distress during intravenous cannulation in children: a double-blind, randomized, placebo-controlled trial

et al. 2022

View full text Add to dashboard Cite

Background: Ketamine is widely used in infants and young children for procedural sedation and anesthesia. The aim of this study was to evaluate the efficacy and safety of low dose oral ketamine to control pain and distress in children during intravenous (IV) cannulation. Methods: This is a prospective, randomized, double-blind study, including children aged between 3 and 6 years requiring a non-emergent IV-line placement. Children were randomly assigned to two groups, treated either with oral ketamine or a placebo. All patients were monitored for vital signs. Pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wong-Baker Faces Pain Rating Scale (WBFS) scales and sedation using a 5-point sedation score. The facility of IV-line placement was measured by a 3-point scale. Adverse effects were recorded after 1 and 24 hours. Results: A total of 79 and 81 children were entered in the ketamine and placebo groups, respectively. The heart and respiratory rates increased significantly in the placebo group. The median CHEOPS 4 (95% confidence interval [CI]: 3, 4, P < 0.001) and WBFS 6 (95% CI: 4, 6, P < 0.001) scores decreased statistically in the ketamine group. IV-line placement was 50% easier in the ketamine group (95% CI: 37%, 63%, P < 0.001). No serious adverse effects were observed in all cases. Conclusions: Low dose oral ketamine effectively decreased the pain and distress during IV cannulation in children without any significant adverse reactions.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of low dose oral ketamine for controlling pain and distress during intravenous cannulation in children: a double-blind, randomized, placebo-controlled trial

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Ketamine is rapidly bio‐transformed in the liver by cytochrome P450 (CYP3A4 and CYP2B6/3A6) to several metabolites, most importantly HNK . These metabolites have a lower or no affinity for the NMDAR, however, similar to ketamine, there is an activation of mTOR .…”

Section: Discussionmentioning

confidence: 99%

The novel antidepressant ketamine enhances dentate gyrus proliferation with no effects on synaptic plasticity or hippocampal function in depressive‐like rats

et al. 2018

View full text Add to dashboard Cite

Aim:Major depressive disorder is a common and debilitating condition with substantial economic impact. Treatment options, although effective, are aimed at relieving the symptoms with limited disease modification. Ketamine, a commonly used anaesthetic, has received substantial attention as it shows rapid antidepressant effects clinically. We studied the effects of ketamine on hippocampal function and dentate gyrus proliferation in rats showing a depressive-like phenotype. Methods: Adolescent and adult animals were pre-natally exposed to the glucocorticoid analog dexamethasone, and we verified a depressive-like phenotype using behavioural tests, such as the sucrose preference. We subsequently studied the effects of ketamine on hippocampal synaptic transmission, plasticity and dentate gyrus proliferation. In addition, we measured hippocampal glutamate receptor expression. We also tested the ketamine metabolite hydroxynorketamine for NMDA-receptor independent effects. Results: Surprisingly, our extensive experimental survey revealed limited effects of ketamine or its metabolite on hippocampal function in control as well as depressivelike animals. We found no effects on synaptic efficacy or induction of long-term potentiation in adolescent and adult animals. Also there was no difference when comparing the dorsal and ventral hippocampus. Importantly, however, ketamine 24 hours prior to experimentation significantly increased the dentate gyrus proliferation, as revealed by Ki-67 immunostaining, in the depressive-like phenotype. Conclusion: We find limited effects of ketamine on hippocampal glutamatergic transmission. Instead, alterations in dentate gyrus proliferation could explain the antidepressant effects of ketamine.

show abstract

“…Psychotomimetic side effects have been reported with intravenous administration, but do not persist beyond the infusion 14. Oral, sublingual and intranasal ketamine have a decreased side effect profile due to lower bioavailability and rapid metabolism to norketamine 45. Over time, ketamine induces and enhances its own metabolism, and hepatic injury with repeated dosing has been documented.…”

Section: Discussionmentioning

confidence: 99%

New use for an old drug: oral ketamine for treatment-resistant depression

2016

View full text Add to dashboard Cite

Treatment-resistant depression (TRD) is a disabling disorder that can interfere with a patient's capacity to understand and participate in medical care and thus negatively impact individual morbidity and mortality. Hospitalised patients with TRD may require rapid alleviation of severe symptomatology, particularly when suicidal or if unable to participate in care decisions. Ketamine is well known for its anaesthetic effects and its use as a 'street' drug; however, its action as an N-methyl-D-aspartate receptor antagonist makes ketamine a potential therapy for TRD. The majority of studies investigating ketamine for TRD have used intravenous drug delivery, demonstrating benefit for rapid alleviation and sustained response of depression symptoms. Oral ketamine for urgent alleviation of TRD symptoms is less reported. We describe rapid alleviation of severe TRD with oral ketamine in a severely ill postoperative hospitalised patient, and review the current literature on 'off-label' use of ketamine for treatment of refractory depression.

show abstract

Pharmacokinetics of Ketamine and Norketamine After Oral Administration of a Liquid Formulation of Ketamine

Cited by 4 publications

References 16 publications

Efficacy and safety of low dose oral ketamine for controlling pain and distress during intravenous cannulation in children: a double-blind, randomized, placebo-controlled trial

Efficacy and safety of low dose oral ketamine for controlling pain and distress during intravenous cannulation in children: a double-blind, randomized, placebo-controlled trial

The novel antidepressant ketamine enhances dentate gyrus proliferation with no effects on synaptic plasticity or hippocampal function in depressive‐like rats

New use for an old drug: oral ketamine for treatment-resistant depression

Contact Info

Product

Resources

About