ArticleCPT: pharmacometrics & systems pharmacology2018
Semimechanistic Population Pharmacokinetic Model to Predict the Drug-Drug Interaction Between S-ketamine and Ticlopidine in Healthy Human Volunteers.
Article in CPT: pharmacometrics & systems pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Pharmacokinetics and pharmacodynamics of intravenous and oral (S)-ketamine: Investigating metabolite contribution to subjective effects.British journal of clinical pharmacology · 2026Trial
- Population Pharmacokinetics of Esketamine Nasal Spray and its Metabolite Noresketamine in Healthy Subjects and Patients with Treatment-Resistant Depression.Clinical pharmacokinetics · 2021Trial
- Population Modelling of Dexmedetomidine Pharmacokinetics and Haemodynamic Effects After Intravenous and Subcutaneous Administration.Clinical pharmacokinetics · 2020Trial
- Article
- Article
- Esketamine: a glimmer of hope in treatment-resistant depression.European archives of psychiatry and clinical neuroscience · 2021Review
- Could ketamine be the answer to treating treatment-resistant major depressive disorder?General psychiatry · 2020Review
- Esketamine: new hope for the treatment of treatment-resistant depression? A narrative review.Therapeutic advances in drug safety · 2020Review
- Intranasal Esketamine (SpravatoP & T : a peer-reviewed journal for formulary management · 2019Article
- Simultaneous Semi-Mechanistic Population Pharmacokinetic Modeling Analysis of Enalapril and Enalaprilat Serum and Urine Concentrations From Child Appropriate Orodispersible Minitablets.Frontiers in pediatrics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low-dose oral S-ketamine is increasingly used in chronic pain therapy, but extensive cytochrome P450 (CYP) mediated metabolism makes it prone to pharmacokinetic drug-drug interactions (DDIs). In our study, concentration-time data from five studies were used to develop a semimechanistic model that describes the ticlopidine-mediated inhibition of S-ketamine biotransformation. A mechanistic model was implemented to account for reversible and time-dependent hepatic CYP2B6 inactivation by ticlopidine, which causes elevated S-ketamine exposure in vivo. A pharmacokinetic model was developed with gut wall and hepatic clearances for S-ketamine, its primary metabolite norketamine, and ticlopidine. Nonlinear mixed effects modeling approach was used (NONMEM version 7.3.0), and the final model was evaluated with visual predictive checks and the sampling-importance-resampling procedure. Our final model produces biologically plausible output and demonstrates that ticlopidine is a strong inhibitor of CYP2B6 mediated S-ketamine metabolism. Simulations from our model may be used to evaluate chronic pain therapy with S-ketamine.
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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.