Estimation of plasma protein binding of selected antipsychotics using computed molecular properties

The plasma protein binding (PPB) data of twelve antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, chlorpromazine, flupentixol, fluphenazine, haloperidol, zuclopenthixol) were estimated using computed molecular descriptors, which included the electronic descriptor – polar surface area (PSA), the constitutional parameter – molecular weight (Mw), the geometric descriptor – volume value (Vol), the lipophilicity descriptor (logP) and aqueous solubility data (logS), and the acidity descriptor (pKa). The relationships between computed molecular properties of the selected antipsychotics and their PPB data were investigated by simple linear regression analysis. Low correlations were obtained between the PPB data of the antipsychotics and PSA, Mw, Vol, pKa, logS (R <0.30) values, while relatively higher correlations (0.35 < R2 < 0.70) were obtained for the majority of logP values. Multiple linear regression (MLR) analysis was applied to access reliable correlations of the PPB data of the antipsychotics and the computed molecular descriptors. Relationships with acceptable probability values (P