A cross-validation study on the relationship between central D2 receptor occupancy and serum perphenazine concentration.
BACKGROUND
There is a need for laboratory measures to guide clinical treatment with antipsychotic drugs. For serum concentration of the classical antipsychotic drug perphenzine an optimal therapeutic interval has been identified between 2 and 6 nmol/l. Positron emission tomography (PET) studies have suggested an optimal interval in central dopamine D2 receptor occupancy of between 65 and 80%.


OBJECTIVE
The aim of the present cross-validation study in clinically stable schizophrenic patients was to examine the relationship between the optimal interval in central D2 receptor occupancy and the therapeutic window for serum perphenazine concentration.


METHODS
Six patients who had responded to maintenance treatment with perphenazine decanoate were examined with PET and [11C]raclopride during steady-state conditions. Blood sampling was carried out for minimum serum perphenazine concentration and during the PET examination. RESULTS. The serum perphenazine concentration was between 1.8 and 9 nmol/l and the D2 receptor occupancy varied between 66 and 82%. The relationship between central receptor occupancy and serum drug concentration was curvilinear. Mild extrapyramidal symptoms were present in the patient with the highest D2 receptor occupancy. CONCLUSIONS. The previously suggested therapeutic window in serum perphenazine concentration is in good agreement with the optimal interval suggested for central D2 receptor occupancy. Serum concentrations at low dose levels may therefore serve as a useful tool in clinical monitoring of antipsychotic drug treatment.
Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, S-171 76 Stockholm, Sweden. Mirjam.Talvik@cns.ki.se
Mirjam
M
Talvik
Anna-Lena
AL
Nordström
Niels-Erik
NE
Larsen
Aurelija
A
Jucaite
Simon
S
Cervenka
Christer
C
Halldin
Lars
L
Farde
D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010546:Perphenazine / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D010546:Perphenazine