A cross-validation study on the relationship between central D-2 receptor occupancy and serum perphenazine concentration

• Rationale: 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 D-2 receptor occupancy of between 65 and 80%. Objectives: The aim of the present cross-validation study in clinically stable schizophrenic patients was to examine the relationship between the optimal interval in central D-2 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 [C-11]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 D-2 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 D-2 receptor occupancy. Conclusions: The previously suggested therapeutic window in serum perphenazine concentration is in good agreement with the optimal interval suggested for central D-2 receptor occupancy. Serum concentrations at low dose levels may therefore serve as a useful tool in clinical monitoring of antipsychotic drug treatment.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

antipsychotics

PANSS

EPS

threshold

therapeutic window

serum concentration

occupancy

dopamine

D-2 receptor

striatum

schizophrenia

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)