Pharmacokinetics and D2 receptor occupancy of long-acting injectable risperidone (Risperdal Consta™) in patients with schizophrenia

• Published in: The international journal of neuropsychopharmacology Vol. 8; no. 1; pp. 27 - 36
• Main Authors: Gefvert, Ola, Eriksson, Bo, Persson, Per, Helldin, Lars, Björner, Annika, Mannaert, Erik, Remmerie, Bart, Eerdekens, Mariëlle, Nyberg, Svante
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.03.2005; Oxford University Press
• Subjects: Administration, Oral; Adult; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - pharmacokinetics; Binding, Competitive - drug effects; Brain - diagnostic imaging; Delayed-Action Preparations; Dopamine Antagonists - administration & dosage; Dopamine Antagonists - pharmacokinetics; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Image Processing, Computer-Assisted; Injections, Intramuscular; Isoxazoles - blood; Male; Middle Aged; Paliperidone Palmitate; Positron-Emission Tomography; Pyrimidines - blood; Radioimmunoassay; Receptors, Dopamine D2 - metabolism; Risperidone - administration & dosage; Risperidone - pharmacokinetics; Schizophrenia - blood; Schizophrenia - drug therapy; Scintillation Counting; pharmacokinetics; receptors; long-acting risperidone; Dopamine D2
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145704004924

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.