Trial reportClinical pharmacokinetics2021
Population Pharmacokinetics of Esketamine Nasal Spray and its Metabolite Noresketamine in Healthy Subjects and Patients with Treatment-Resistant Depression.
Trial report in Clinical pharmacokinetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 13 registered trials, which are not on this map. Cited by 38 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Single-Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Subjects
An Open-label, Single-Dose Study to Assess the Pharmacokinetics, Safety and Tolerability of Intranasally Administered Esketamine in Healthy Japanese and Caucasian Subjects
A Double-Blind, Doubly-Randomized, Placebo-Controlled Study of Intranasal Esketamine in an Adaptive Treatment Protocol to Assess Safety and Efficacy in Treatment-Resistant Depression (SYNAPSE)
An Open-Label, Single-Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Elderly and Adult Subjects
A Double-blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Subjects Who Are Assessed to be at Imminent Risk for Suicide
An Open-Label Study to Evaluate the Absolute Bioavailability of Intranasal and Oral Esketamine and the Effects of Clarithromycin on the Pharmacokinetics of Intranasal Esketamine in Healthy Subjects
An Open-Label, Single-Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Elderly (>= 75 Years of Age) and Healthy Younger Adult Subjects (18 to 55 Years of Age, Inclusive)
A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subjects With Treatment-resistant Depression
A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subjects With Treatment-resistant Depression
A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Intranasal Esketamine Plus an Oral Antidepressant in Elderly Subjects With Treatment-resistant Depression
An Open-Label Study to Evaluate the Pharmacokinetics of Intranasal Esketamine and Its Effects on the Pharmacokinetics of Orally-Administered Midazolam and Bupropion in Healthy Subjects
A Single-Center, Single-Dose, Double-Blind, Double-Dummy, Placebo-Controlled, Randomized Crossover Study to Evaluate the Abuse Potential of Intranasal Esketamine Compared to Racemic Intravenous Ketamine in Nondependent, Recreational Users of Perception-Altering Drugs
An Open-Label, Single-Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Han Chinese, Korean, Japanese, and Caucasian Subjects and the Effects of Rifampin on the Pharmacokinetics of Intranasally Administered Esketamine
Who cites it
38 citing papers in PubMed, 3 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Dose-dependent adverse events of esketamine in treatment-resistant depression: a systematic review and meta-analysis of randomized controlled trials.Frontiers in pharmacology · 2026Pooled it
- Exploration of current situation of psychotropic drugs research and development in China based on drug clinical trials.Frontiers in psychiatry · 2025Pooled it
- Evidence for the beneficial effect of ketamine in the treatment of patients with post-traumatic stress disorder: A systematic review and meta-analysis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Pooled it
- Pharmacokinetics and pharmacodynamics of intravenous and oral (S)-ketamine: Investigating metabolite contribution to subjective effects.British journal of clinical pharmacology · 2026Trial
- Prophylactic esketamine to reduce postpartum depression in primiparae: A multicentre, double-blind, randomised clinical trial.European journal of anaesthesiology · 2026Trial
- Low-dose esketamine for postoperative fatigue after gynecological laparoscopic surgery: a randomized controlled trial.BMC anesthesiology · 2026Trial
- The role of cytochrome P450 polymorphisms in the pharmacokinetics of oral esketamine.The pharmacogenomics journal · 2026Trial
- The Median Effective Infusion Rate of Ciprofol with Different Doses of Esketamine During Gastrointestinal Endoscopy: A Randomized Controlled Trial.Drug design, development and therapy · 2026Trial
- Effect of Anterior Quadratus Lumborum Block at the Lateral Supra-Arcuate Ligament Combined with Esketamine on the Quality of Postoperative Recovery After Laparoscopic Radical Surgery for Elderly Patients with Colorectal Cancer: A Randomized Controlled Trial.Drug design, development and therapy · 2026Trial
- Effect of esketamine on postpartum depression after labor analgesia and potential mechanisms: a randomized, double-blinded controlled trial.BMC anesthesiology · 2024Trial
- Determining the effective dose of esketamine for mitigating pain during propofol injection by Dixon's up-and-down method: a double-blind, prospective clinical study of drug dose response.BMC anesthesiology · 2022Trial
- A crucial cautionary note on frequently incorrect dose equivalence between ketamine and esketamine.Molecular psychiatry · 2026Article
- Esketamine during anesthesia induction improves early postoperative sleep quality in female patients undergoing laparoscopic surgery: A randomized trial.Pakistan journal of medical sciences · 2026Article
- Bifunctional Modulation of NMDA and Opioid Receptors in Ketamine Reinforcement and Misuse: Implications for Substance Use Disorder Treatment.Biological psychiatry · 2026Review
- Esketamine Nasal Spray: Mechanism of Action, Clinical, and Translational Science.Clinical and translational science · 2026Review
- Clinical applications of esketamine: Current status and future perspectives.The Journal of international medical research · 2026Review
- Pilot study on esketamine response in treatment-resistant depression: impact of pharmacogenetic, clinical, and demographic variables.Frontiers in pharmacology · 2026Article
- Ketamine-Occasioned Mystical Experience in Veterans with Treatment-Resistant Depression: A Retrospective Exploratory Analysis.Psychedelic medicine (New Rochelle, N.Y.) · 2025Article
- Ketamine-From an Anesthetic to a Psychiatric Drug: Mechanisms of Action, Clinical Applications and Potential Risks.Molecules (Basel, Switzerland) · 2025Review
- Auto-Induction in Oral Esketamine Treatment for Treatment-Resistant Depression: An Exploratory Study.Pharmaceuticals (Basel, Switzerland) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEsketamine nasal spray is approved for treatment-resistant depression.
objectiveThe objective of this study was to characterize the pharmacokinetics of esketamine and noresketamine in healthy subjects and patients with treatment-resistant depression.
methodsEsketamine and noresketamine were measured in > 9000 plasma samples collected from 820 individuals who received esketamine by the intranasal, intravenous, and oral routes. An open linear model for esketamine (three compartments) and noresketamine (two compartments) that included a hepato-portal compartment was developed using NONMEM
resultsThe fraction of a 28-mg intranasal dose absorbed through the nasal cavity (FR
conclusionsEsketamine and noresketamine pharmacokinetics was successfully characterized in healthy subjects and patients with treatment-resistant depression. The model quantified esketamine absolute nasal and oral bioavailability, its hepatic flow-limited clearance and biotransformation to the major metabolite noresketamine, and the influence of intrinsic and extrinsic factors on esketamine pharmacokinetics. Clinical trials registration numbers of the studies included in the analysis: ESKETINTRD1001 (NCT01780259), ESKETINTRD1002 (NCT01980303), ESKETINTRD1003 (NCT02129088), ESKETINTRD1008 (NCT02846519), ESKETINTRD1009 (NCT02343289), ESKETINTRD1010 (NCT02568176), ESKETINTRD1012 (NCT02345148), 54135419TRD1015 (NCT02682225), ESKETINTRD2003 (NCT01998958), ESKETINSUI2001 (NCT02133001), ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585), and ESKETINTRD3005 (NCT02422186).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.