Ketone reductase activity and reduced haloperidol/haloperidol ratios in haloperidol-treated schizophrenic patients

Twenty schizophrenic patients were treated with a fixed haloperidol (HL) dose of 20 mg/day for 4 weeks. The conversion of HL to its reduced metabolite (reduced haloperidol, RH) occurs via the ketone reductase enzyme. RH is also converted back to HL by the cytochrome P450 2D6 isozyme. Ketone reductas...

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Bibliographic Details
Published in:Psychiatry research 1995-07, Vol.57 (2), p.101-108
Main Authors: Huang, Huang-Fuh, Jann, Michael W., Tseng, Yung-Te, Chung, Ming-Cheng, Chien, Ching-Piao, Chang, Wen-Ho
Format: Article
Language:English
Subjects:
Adult
Antipsychotic Agents - blood
Antipsychotic Agents - pharmacokinetics
Antipsychotic Agents - therapeutic use
Biological and medical sciences
Debrisoquin hydroxylase
Dose-Response Relationship, Drug
Erythrocytes
Female
Haloperidol - blood
Haloperidol - pharmacokinetics
Haloperidol - therapeutic use
Humans
Ketone Oxidoreductases - metabolism
Male
Medical sciences
Neuroleptic treatment
Neuropharmacology
Pharmacokinetics
Pharmacology. Drug treatments
Psycholeptics: tranquillizer, neuroleptic
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Red blood cells
Schizophrenia - drug therapy
Schizophrenia - metabolism
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Summary:Twenty schizophrenic patients were treated with a fixed haloperidol (HL) dose of 20 mg/day for 4 weeks. The conversion of HL to its reduced metabolite (reduced haloperidol, RH) occurs via the ketone reductase enzyme. RH is also converted back to HL by the cytochrome P450 2D6 isozyme. Ketone reductase activity can be measured in red blood cells. Plasma HL and RH levels were assayed by high performance liquid chromatography. Blood samples were obtained at baseline and during weeks 2 and 4 of HL therapy. Seventeen of 20 patients had ketone reductase values < 3. A significant correlation between ketone reductase activity and RH/HL plasma ratios was observed at week 4 in these 17 patients. Patients with ketone reductase activity |>3 could represent a subgroup of patients that metabolize HL differently. The wide interpatient variability observed with HL and RH plasma levels in HL-treated patients could reflect differences in ketone reductase activity and the metabolic status of debrisoquin hydroxylase (cytochrome P450IID6) in psychiatric patients.
ISSN:0165-1781
1872-7123
DOI:10.1016/0165-1781(95)02633-8