The International Journal of Neuropsychopharmacology



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


Ola Gefvert a1c1, Bo Eriksson a2, Per Persson a3, Lars Helldin a3, Annika Björner a4, Erik Mannaert a5, Bart Remmerie a5, Mariëlle Eerdekens a5 and Svante Nyberg a6
a1 Centre for Clinical Research, University of Uppsala, Central Hospital Västerås, Sweden
a2 Johnson & Johnson Pharmaceutical Research and Development, Division of Janssen-Cilag AB, Sollentuna, Sweden
a3 Department of Psychiatry, Norra Älvsborgs Läns Landsting, Sweden
a4 Department of Psychiatry, Göteborg University Hospital, Sweden
a5 Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium
a6 Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden

Article author query
gefvert o   [PubMed][Google Scholar] 
eriksson b   [PubMed][Google Scholar] 
persson p   [PubMed][Google Scholar] 
helldin l   [PubMed][Google Scholar] 
bjorner a   [PubMed][Google Scholar] 
mannaert e   [PubMed][Google Scholar] 
remmerie b   [PubMed][Google Scholar] 
eerdekens m   [PubMed][Google Scholar] 
nyberg s   [PubMed][Google Scholar] 

Abstract

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.

(Received April 2 2004)
(Reviewed June 18 2004)
(Revised August 4 2004)
(Accepted August 15 2004)


Key Words: Dopamine D2; long-acting risperidone; pharmacokinetics; receptors.

Correspondence:
c1 Dr O. Gefvert, Centre for Clinical Research, University of Uppsala, Central Hospital, S-721 89 Västerås, Sweden. Tel.: +46 21 17 3369 Fax: +46 21 17 5914 E-mail: ola.gefvert@ltvastmanland.se


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