Plasma protein binding of perazine and amitriptyline in psychiatric patients.
The free fraction of amitriptyline (AT), measured by equilibrium dialysis in plasma from 29 AT-treated depressed patients, was 5.4-9.8% (mean 7.7%), which was the same as the values in 26 healthy controls (4.9-9.6%, mean 7.6%). The plasma levels of lipoproteins, as reflected by total cholesterol, and of alpha 1-acid glycoprotein (alpha 1-AGP) did not differ between the two groups. the free fraction of AT in both exhibited a significant negative correlation with the concentrations of those two proteins. The unbound fraction of perazine (PER) was the same (3.1-5.9%, mean 4.4%) in plasma from 22 schizophrenic patients and from 24 healthy volunteers (2.9-6.0%, mean 4.5%). However, in patient plasma alpha 1-AGP was significantly higher (mean 1.07 vs 0.81 mg/ml) and total cholesterol tended to be lower (mean 173 vs 201 mg/100 ml) than in plasma from normals. In consequence, the free fraction of PER was negatively correlated with the alpha 1-AGP concentration in plasma from patients and with the cholesterol level in plasma from control subjects; the other correlations were not significant. In 7 patients, the alpha 1-AGP level was normal prior to Per treatment. Serial blood samples from 6 patients revealed a consistent elevation of alpha 1-AGP above its pretreatment level during 4 weeks of PER administration in 5 of the subjects and a transient increase in one other. while low lipoprotein levels in schizophrenics seem to be a disease-related trait, the increase of alpha 1-AGP may be a drug effect.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000639:Amitriptyline / Q000097:blood* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010464:Perazine / Q000097:blood* / Q000627:therapeutic use; D011485:Protein Binding; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy
D014150:Antipsychotic Agents; D001798:Blood Proteins; D008074:Lipoproteins; D000639:Amitriptyline; D010464:Perazine