Faculty Opinions recommendation of 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.

2012 ◽  
Author(s):  
John Davis
Keyword(s):  
Positron Emission Tomography ◽  
Single Dose ◽  
Steady State ◽  
Receptor Antagonist ◽  
Healthy Subjects ◽  
Receptor Occupancy ◽  
Emission Tomography ◽  
Dose Selection ◽  
Positron Emission

scholarly journals An open-label, positron emission tomography study of the striatal D2/D3 receptor occupancy and pharmacokinetics of single-dose oral brexpiprazole in healthy participants

2020 ◽  
Author(s):  
Dean F. Wong ◽  
Arash Raoufinia ◽  
Patricia Bricmont ◽  
James R. Brašić ◽  
Robert D. McQuade ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Single Dose ◽  
Caudate Nucleus ◽  
Receptor Occupancy ◽  
Emission Tomography ◽  
Maximum Plasma ◽  
Open Label ◽  
Post Dose ◽  
Positron Emission ◽  
Healthy Participants

Abstract Purpose The aim of this Phase 1, open-label, positron emission tomography (PET) study was to determine the degree of striatal D2/D3 receptor occupancy induced by the serotonin–dopamine activity modulator, brexpiprazole, at different single dose levels in the range 0.25–6 mg. Methods Occupancy was measured at 4 and 23.5 h post-dose using the D2/D3 receptor antagonist [11C]raclopride. The pharmacokinetics, safety and tolerability of brexpiprazole were assessed in parallel. Results Fifteen healthy participants were enrolled (mean age 33.9 years; 93.3% male). Mean D2/D3 receptor occupancy in the putamen and caudate nucleus increased with brexpiprazole dose, leveled out at 77–88% with brexpiprazole 5 mg and 6 mg at 4 h post-dose, and remained at a similar level at 23.5 h post-dose (74–83%). Estimates of maximum obtainable receptor occupancy (Omax) were 89.2% for the putamen and 95.4% for the caudate nucleus; plasma concentrations predicted to provide 50% of Omax (EC50) were 8.13 ng/mL and 7.75 ng/mL, respectively. Brexpiprazole area under the concentration–time curve (AUC∞) and maximum plasma concentration (Cmax) increased approximately proportional to dose. No notable subjective or objective adverse effects were observed in this cohort. Conclusion By extrapolating the observed single-dose D2/D3 receptor occupancy data in healthy participants, multiple doses of brexpiprazole 2 mg/day and above are expected to result in an efficacious brexpiprazole concentration, consistent with clinically active doses in schizophrenia and major depressive disorder. Trial registration ClinicalTrials.gov NCT00805454 December 9, 2008.

Phase 1 positron emission tomography (PET) study of the receptor occupancy of rolapitant, a novel NK-1 receptor antagonist.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e20690-e20690 ◽  
Author(s):  
Allen Poma ◽  
Jennifer Christensen ◽  
Jennifer Davis ◽  
Vikram Kansra ◽  
Robert E. Martell ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Receptor Antagonist ◽  
Phase 1 ◽  
Receptor Occupancy ◽  
Emission Tomography ◽  
Positron Emission
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