Interindividual variation in bromperidol metabolism and relationship to therapeutic effects.
Plasma concentrations of bromperidol (BRP) and reduced bromperidol (RBRP) were determined in 31 patients with schizophrenia who were administered BRP for their psychiatric symptoms. Activities of carbonyl reductase in red blood cells were assayed using BRP as a substrate. Plasma concentrations of BRP and RBRP ranged from 2.2 to 23.5 ng/mL and from 0.2 to 8.2 ng/mL, respectively. RBRP-to-BRP ratios in plasma ranged from 0.01 to 0.94 (mean +/- SD: 0.31 +/- 0.20), values notably lower than the previously reported values of reduced haloperidol to haloperidol (HAL) in the plasma from patients on HAL. The activity of BRP reductase in red blood cells was determined as 6.8-12.3 pmol/hr/10(6) red blood cells, which was at approximately the same level as that of HAL reductase. Patients with positive responses to BRP treatment were evaluated using the Brief Psychiatric Rating Scale. We found that the number of patients who had a positive response to BRP did not increase after BRP plasma levels had reached the level of 12 ng/mL. This finding suggests that a therapeutic plateau in BRP pharmacotherapy of schizophrenia occurs, and there is no advantage to raising the dose once this plateau is reached.
Someya
T
T
Department of Psychiatry, Niigata University School of Medicine, Asahimachi, Japan. someya@med.niigata-u.ac.jp
Muratake
T
T
Hirokane
G
G
Shibasaki
M
M
Shimoda
K
K
Takahashi
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007206:Individuality; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D006220:Haloperidol; C006820:bromperidol