A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone.
OBJECTIVE
Long-acting injectable risperidone represents the first clinically available depot atypical antipsychotic. The present study used positron emission tomography (PET) to evaluate its dopamine D(2) binding profile at doses of 25, 50, or 75 mg administered every 2 weeks.


METHODS
After achieving stabilization with one of the doses, nine patients with a diagnosis of schizophrenia or schizoaffective disorder underwent [(11)C]raclopride PET to measure D(2) occupancy. Participants were scanned twice during the 2-week injection interval: within 3 days after injection (postinjection) and within 5 days before the next injection (preinjection). At the same time, plasma was collected for measurements of risperidone plus 9-hydroxyrisperidone.


RESULTS
Mean post- and preinjection D(2) occupancy levels for the 25-, 50-, and 75-mg doses were 71.0% and 54.0%, 74.4% and 65.4%, and 81.5% and 75.0%, respectively. There was a significant correlation between dose and plasma concentrations of risperidone plus 9-hydroxyrisperidone, and the estimated plasma concentration associated with 50% D(2) occupancy (ED(50)) was 11.06 ng/ml. Prolactin levels were not correlated with drug levels or D(2) occupancy.


CONCLUSIONS
All three doses of injectable risperidone showed peak D(2) occupancy levels above the 65% threshold associated with optimal clinical response; the 75-mg dose approximated the 80% threshold linked to increased risk of extrapyramidal symptoms. Doses of 25 or 50 mg should provide therapeutic efficacy while minimizing the risk of extrapyramidal symptoms.
Remington
Gary
G
Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, Ont. M5T 1R8, Canada. gary_remington@camh.net
Mamo
David
D
Labelle
Alain
A
Reiss
Jeffrey
J
Shammi
Chekkera
C
Mannaert
Erik
E
Mann
Steve
S
Kapur
Shitij
S
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000517:prevention & control; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007267:Injections; D007555:Isoxazoles / Q000097:blood; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D049268:Positron-Emission Tomography; D011388:Prolactin / Q000097:blood; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D011743:Pyrimidines / Q000097:blood; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D018967:Risperidone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism
D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D003692:Delayed-Action Preparations; D007555:Isoxazoles; D011743:Pyrimidines; D017448:Receptors, Dopamine D2; D020891:Raclopride; D011388:Prolactin; D018967:Risperidone; D000068882:Paliperidone Palmitate