Pharmacokinetics and D2 receptor occupancy of long-acting injectable risperidone (Risperdal Consta) in patients with schizophrenia.
Thirteen patients with schizophrenia received injections of 25, 50, or 75 mg of long-acting risperidone every 2 wk. Brain D2 receptor occupancy was assessed with [11C]raclopride 2 wk after the last (fifth) injection (day 71) in seven subjects and 2 wk after the third injection (day 44) in one subject. Stable plasma concentrations were reached after the third injection and steady-state concentrations of the active moiety (risperidone + 9-hydroxyrisperidone) after the fourth injection. Steady-state plasma concentrations were maintained for 4-5 wk after the last injection and then declined rapidly. After injections of 25, 50 and 75 mg on day 44 or day 71, D2 receptor occupancy ranged from 25-48%, 59-83% and 62-72% respectively, while plasma active-moiety levels ranged from 4.4-8.8, 15.0-31.1 and 22.5-26.3 ng/ml respectively. The results indicate that brain D2 receptor occupancy at steady state after injections of long-acting risperidone was in the range found in patients effectively treated with 2-6 mg of oral risperidone.
Gefvert
Ola
O
Centre for Clinical Research, University of Uppsala, Central Hospital Västerås, Sweden. ola.gefvert@ltvastmanland.se
Eriksson
Bo
B
Persson
Per
P
Helldin
Lars
L
Björner
Annika
A
Mannaert
Erik
E
Remmerie
Bart
B
Eerdekens
Mariëlle
M
Nyberg
Svante
S
D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging*; D003692:Delayed-Action Preparations; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007273:Injections, Intramuscular; D007555:Isoxazoles / Q000097:blood; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D049268:Positron-Emission Tomography; D011743:Pyrimidines / Q000097:blood; D011863:Radioimmunoassay; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018967:Risperidone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012588:Scintillation Counting
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D018492:Dopamine Antagonists; D007555:Isoxazoles; D011743:Pyrimidines; D017448:Receptors, Dopamine D2; D018967:Risperidone; D000068882:Paliperidone Palmitate