A cross-validation study on the relationship between central D2 receptor occupancy and serum perphenazine concentration

Abstract

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.

CYP2D6 genotype in relation to perphenazine concentration and pituitary pharmacodynamic tissue sensitivity in Asians: CYP2D6–serotonin–dopamine crosstalk revisited

“…In a previous study of clinically stable schizophrenic patients, serum perphenazine concentration was reportedly between 1.8 and 9 nmol/l whereas the D2 receptor occupancy varied between 66 and 82%, as measured by positron emission tomography [43]. Moreover, there was a curvilinear correlation between perphenazine concentration and D2 receptor occupancy [43].…”

“…Moreover, there was a curvilinear correlation between perphenazine concentration and D2 receptor occupancy [43]. This indicates that the D2 receptor that mediates prolactin response to antipsychotic drugs is not saturated within this perphenazine concentration range (1.8-9.0 nmol/l) [43]. The range of C max values of perphenazine in this study (0.36-6.90 nmol/l) are well within (in fact lower than) the concentration range observed in the earlier study noted above [43].…”

“…In a previous study of clinically stable schizophrenic patients, serum perphenazine concentration was reportedly between 1.8 and 9 nmol/l whereas the D2 receptor occupancy varied between 66 and 82%, as measured by positron emission tomography [43]. Moreover, there was a curvilinear correlation between perphenazine concentration and D2 receptor occupancy [43]. This indicates that the D2 receptor that mediates prolactin response to antipsychotic drugs is not saturated within this perphenazine concentration range (1.8-9.0 nmol/l) [43].…”

Serotonin transporter occupancy induced by paroxetine in patients with major depression disorder: a 123I-ADAM SPECT study

“…However, scanning a patient in the naïve-or drug-free condition is difficult and too often unfeasible. For this reason, calculation of receptor occupancies using the mean receptor availability value from a control group is extensively used in the literature either using SPECT (Knable et al 1997;Dresel et al 1999;Tauscher et al 1999a) or PET (Gefvert et al 1998;Kapur et al 1999;Talvik et al 2004). The control group can either be an independent group of patients with the same characteristics as the target population or a group of healthy subjects under the assumption that there are no differences in receptor or transporter availability between healthy subjects and the patient population.…”

P-Glycoprotein Influence on the Brain Uptake of a 5-HT2A Ligand: [18F]MH.MZ

“…These advances improved substantially the understanding of the mechanisms underlying the antipsychotic effects of D 2 and 5HT 2 receptor antagonists [8] . However, these studies referred primarily to the dopaminergic activity [9] .…”