Trial reportJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2012
Predicting brain occupancy from plasma levels using PET: superiority of combining pharmacokinetics with pharmacodynamics while modeling the relationship.
Trial report in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Therapeutic Reference Range for Aripiprazole in Schizophrenia Revised: a Systematic Review and Metaanalysis.Psychopharmacology · 2022Pooled it
- Prediction of a clinically effective dose of THY1773, a novel VBiopharmaceutics & drug disposition · 2021Trial
- An investigation into aripiprazole's partial D₂ agonist effects within the dorsolateral prefrontal cortex during working memory in healthy volunteers.Psychopharmacology · 2016Trial
- The relationship between antipsychotic D2 occupancy and change in frontal metabolism and working memory : A dual [(11)C]raclopride and [(18) F]FDG imaging study with aripiprazole.Psychopharmacology · 2013Trial
- Relationship between subjective well-being and aripiprazole: an [Scientific reports · 2022Article
- Molecular Imaging of Dopamine Partial Agonists in Humans: Implications for Clinical Practice.Frontiers in psychiatry · 2022Review
- Clinical Pharmacokinetics and Pharmacodynamics of Drugs in the Central Nervous System.Clinical pharmacokinetics · 2018Review
- Contrast-enhanced dual mode imaging: photoacoustic imaging plus more.Biomedical engineering letters · 2017Review
- Regional Differences in Serotonin Transporter Occupancy by Escitalopram: An [Clinical pharmacokinetics · 2017Article
- In-depth neuropharmacokinetic analysis of antipsychotics based on a novel approach to estimate unbound target-site concentration in CNS regions: link to spatial receptor occupancy.Molecular psychiatry · 2016Article
- Simulation of PET scan timings for receptor occupancy studies of CNS drugs: a simple fixed-time design performed as well as scattered time point designs.European journal of clinical pharmacology · 2015Article
- Presynaptic dopaminergic function: implications for understanding treatment response in psychosis.CNS drugs · 2014Review
- Understanding the hysteresis loop conundrum in pharmacokinetic/pharmacodynamic relationships.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2014Article
- Midbrain dopamine function in schizophrenia and depression: a post-mortem and positron emission tomographic imaging study.Brain : a journal of neurology · 2013Article
- Molecular imaging as a guide for the treatment of central nervous system disorders.Dialogues in clinical neuroscience · 2013Review
- Translational PK-PD modeling in pain.Journal of pharmacokinetics and pharmacodynamics · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Positron emission tomography (PET) studies of dopamine receptor occupancy can be used to assess dosing of antipsychotics. Typically, studies of antipsychotics have applied pharmacodynamic (PD) modeling alone to characterize the relationship between antipsychotic dose and its effect on the brain. However, a limitation of this approach is that it does not account for the discrepancy between the time courses of plasma concentration and receptor occupancy by antipsychotics. Combined pharmacokinetic-PD (PK-PD) modeling, by incorporating the time dependence of occupancy, is better suited for the reliable analysis of the concentration-occupancy relationship. To determine the effect of time on the concentration-occupancy relationship as a function of analysis approach, we measured dopamine receptor occupancy after the administration of aripiprazole using [(11)C]raclopride PET and obtained serial measurements of the plasma aripiprazole concentration in 18 volunteers. We then developed a PK-PD model for the relationship, and compared it with conventional approach (PD modeling alone). The hysteresis characteristics were observed in the competitor concentration-occupancy relationship and the value of EC(50) was different according to the analysis approach (EC(50) derived from PD modeling alone=11.1 ng/mL (95% confidence interval (CI)=10.1 to 12.1); while that derived from combined PK-PD modeling=8.63 ng/mL (95% CI=7.75 to 9.51)). This finding suggests that PK-PD modeling is required to obtain reliable prediction of brain occupancy by antipsychotics.
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.