Plasma alpha-one acid glycoprotein and haloperidol concentrations in schizophrenic patients.
Thirty six schizophrenic patients were randomly assigned to placebo or haloperidol treatment for 6 weeks. Blood samples to measure plasma alpha-one acid glycoprotein (AAG), haloperidol and reduced haloperidol concentrations were obtained at baseline and weeks 2, 4, and 6. Blood samples were obtained 10-12 h after the evening dose and prior to the morning dose. Haloperidol and reduced haloperidol was assayed by HPLC with electrochemical detection. Plasma AAG levels were assayed by radial immunodiffusion. Patients were clinically assessed by the Brief Psychiatric Rating Scale (BPRS) and Abnormal Involuntary Movement Scale at baseline and weeks 2, 4, and 6. BPRS scores did not significantly decrease during placebo treatment, although a slight drop in plasma AAG levels was found. Haloperidol produced a significant decrease in BPRS scores and plasma AAG levels. Mean plasma haloperidol levels were 12.9 +/- 14.7 ng/ml at week 6. Significant correlations between decreasing BPRS scores and plasma AAG levels were not found with only a strong trend at week 2 (r = 0.445, p = 0.073). The role of AAG and psychotropic drug disposition in psychiatric patients requires further evaluation.
Jann
M W
MW
Mercer University, Southern School of Pharmacy, Atlanta, Ga, USA.
Crabtree
B L
BL
Pitts
W M
WM
Lam
Y W
YW
Carter
J G
JG
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000097:blood; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D009961:Orosomucoid / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D009961:Orosomucoid; C040692:4-(4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl)-1-(4-fluorophenyl)-1-butanol; D006220:Haloperidol