ArticlePsychopharmacology2011
The use of healthy volunteers instead of patients to inform drug dosing studies: a [¹¹C]raclopride PET study.
Article in Psychopharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed.
- Dopaminergic modulation of probabilistic reasoning and overconfidence in errors: a double-blind study.Schizophrenia bulletin · 2014Trial
- Associations between visual perception accuracy and confidence in a dopaminergic manipulation study.Frontiers in psychology · 2015Article
- Presynaptic dopaminergic function: implications for understanding treatment response in psychosis.CNS drugs · 2014Review
- Determination of dopamine D₂ receptor occupancy by lurasidone using positron emission tomography in healthy male subjects.Psychopharmacology · 2013Article
- D₂-receptor occupancy measurement of JNJ-37822681, a novel fast off-rate D₂-receptor antagonist, in healthy subjects using positron emission tomography: single dose versus steady state and dose selection.Psychopharmacology · 2012Article
- Pharmacokinetic modeling of P-glycoprotein function at the rat and human blood-brain barriers studied with (R)-[11C]verapamil positron emission tomography.EJNMMI research · 2012Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
rationaleReceptor occupancy study has been performed to evaluate pharmacokinetic profiles in new antipsychotic drug development. While these findings highlight the value of positron emission tomography (PET) for dose-finding study, what is unclear is if it is necessary to conduct these studies in patients with schizophrenia or whether studies in healthy volunteers are adequate.
objectivesTo determine if it is necessary to conduct dopamine receptor occupancy studies in patients with schizophrenia or whether studies in healthy volunteers are adequate for dose-finding study, we compared the concentration-occupancy relationship in terms of EC(50) between patients and healthy volunteers.
methodsTen healthy volunteers and eight patients with schizophrenia participated in the study. We measured dopamine receptor occupancy using [(11)C]raclopride PET and plasma concentration of YKP1358, a novel antipsychotic drug under clinical development, at a number of time points after the administration of YKP1358. Pharmacokinetic data including area under the plasma concentration versus time curve, elimination half-life, maximum observed plasma concentration, and the time to reach the maximum observed plasma concentration were obtained. We explored the relationship between plasma concentration and dopamine D(2) receptor occupancy using E (max) model and calculated EC(50).
resultsThe elimination half-life was longer in healthy volunteers than in patients. Other pharmacokinetic parameters were not significantly different between two groups. The EC(50) was 7.6 ng/ml (95% confidence interval (CI) 6.2-9.0) in healthy volunteers and 8.6 (95% CI 7.4-9.9) in patients.
conclusionsThe antipsychotic concentration-occupancy relationship in patients can be estimated from the EC(50) data of healthy volunteers.
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