Intranasal Drug Delivery in Neuropsychiatry: Focus on Intranasal Ketamine for Refractory Depression

Andrade, Chittaranjan

doi:10.4088/jcp.15f10026

Cited by 40 publications

(25 citation statements)

References 48 publications

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“…leading to rapidly attained peak blood levels, as observed in this study [3]. Ketamine was completely bioavailable following IN administration.…”

Section: Table 2 Pharmacokinetic Parameters Of Ketamine In Dogs Admisupporting

confidence: 79%

“…This can be partially explained by differences in anatomy of the nasal cavity between humans and dogs. Following intranasal administration, ketamine can be delivered directly to the central nervous system, where it can exert its actions [3,4,46]. This direct nose to brain delivery, bypassing the blood brain barrier, occurs mainly through the olfactory epithelium, which comprises 77% of the nasal cavity in dogs [46].…”

Section: Table 2 Pharmacokinetic Parameters Of Ketamine In Dogs Admimentioning

confidence: 99%

“…Recently, intranasal administration of ketamine has gained attention in human medicine. Intranasal drug administration delivers drugs directly to the central nervous system, bypassing the blood brain barrier and is associated with a fast onset of action [3,4]. In addition, intranasal drug delivery avoids painful parenteral administration.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…leading to rapidly attained peak blood levels, as observed in this study [3]. Ketamine was completely bioavailable following IN administration.…”

Section: Table 2 Pharmacokinetic Parameters Of Ketamine In Dogs Admisupporting

confidence: 79%

Section: Table 2 Pharmacokinetic Parameters Of Ketamine In Dogs Admimentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2020

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“…As an example, the patient could have been advised a trial with an antidepressant such as venlafaxine, mirtazapine, or dothiepin; and augmentation, if necessary, could have been accomplished with an atypical antipsychotic drug such as aripiprazole or olanzapine. Next, had ketamine eventually been considered necessary, it could have been more simply dosed by the intranasal route,[ 2 ] obviating the inconvenience and discomfort associated with venipuncture.…”

mentioning

confidence: 99%

Author′s reply

Andrade¹,

Rao²

2015

Indian J Psychiatry

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“…The intranasal formulation of esketamine has obvious value. It has a rapid onset of action, bypasses the blood-brain barrier, has good bioavailability and is more practical and less r e s o u r c e -d e m a n d i n g t h a n i n t r a v e n o u s administration 10 . The clinical evidence is limited to one RCT containing 20 subjects who were administered a single dose of 50 mg of intranasal esketamine or saline placebo at two time points, one week apart.…”

mentioning

confidence: 99%

Comment on FDA's Breakthrough Therapy Designation of Intranasal Esketamine for the Treatment of Major Depressive Disorder with Imminent Risk of Suicide

Thomas

Çetin

Baker

et al. 2016

Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychophar

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Intranasal Drug Delivery in Neuropsychiatry: Focus on Intranasal Ketamine for Refractory Depression

Cited by 40 publications

References 48 publications

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

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

Author′s reply

Comment on FDA's Breakthrough Therapy Designation of Intranasal Esketamine for the Treatment of Major Depressive Disorder with Imminent Risk of Suicide

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