Depot haloperidol treatment in outpatients with schizophrenia on monotherapy: impact of CYP2D6 polymorphism on pharmacokinetics and treatment outcome.
Haloperidol and several other antipsychotic drugs are at least partially metabolized by the polymorphic cytochrome P450 2D6 (CYP2D6). The interindividual variation in metabolic capacity of CYP2D6 might be of importance when dosing. In this study, 26 outpatients with schizophrenia and depot haloperidol as monotherapy were genotyped. The authors found 1 patient with no functional alleles, 8 with one functional allele, 16 with two functional alleles, and 1 with three functional alleles. The daily dose of haloperidol ranged from 0.45 to 14.29 mg. Steady state plasma concentrations were measured at peak (range, 1.6-67 nmol/L) and at trough (range, 1.0-49 nmol/L). The Positive and Negative Syndrome scale for Schizophrenia and the Extrapyramidal Symptom Rating Scale were used to evaluate the clinical effect. The authors found a clear correlation between haloperidol plasma concentration and number of active CYP2D6 alleles. No correlation was found between plasma concentration of haloperidol or number of CYP2D6 alleles and treatment outcome or side effects. A model to predict plasma concentration from dose and number of active CYP2D6 alleles was formed from the obtained data by means of multiple linear regression.
Department of Laboratory Medicine, Division of Clinical Pharmacology, CI-68 Karolinska University Hospital, SE-141 86 Stockholm, Sweden. Georgios.Panagiotidis@ki.se
Georgios
G
Panagiotidis
Holger W
HW
Arthur
Jonatan D
JD
Lindh
Marja-Liisa
ML
Dahl
Folke
F
Sjöqvist
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006220:Haloperidol / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000188:drug therapy* / Q000201:enzymology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D019389:Cytochrome P-450 CYP2D6; D006220:Haloperidol