The cytochrome P450 CYP1A2 genetic polymorphisms *1F and *1D do not affect clozapine clearance in a group of schizophrenic patients.
BACKGROUND
The atypical antipsychotic drug clozapine is metabolized by CYP1A2. The activity of CYP1A2 is highly variable and is among others dependent on smoking habits. Certain genotypes of CYP1A2 have been associated with increased inducibility/activity of CYP1A2. However, the relevance of genotyping for these mutations in a clinical setting has not yet been demonstrated.


METHODS
In this study, the CYP1A2 *1F, *1C and *1D genotypes of 58 schizophrenic patients on clozapine treatment were correlated with clozapine serum concentrations corrected for dose and weight or concentration/dosage ratios.


RESULTS
The allele frequency of *1F and *1D was 67% and 6%, respectively. With an allele frequency of 1%, the occurrence of *1C was very low. Multivariate analysis of variance did not reveal any significant correlations between CYP1A2 genotypes and clozapine clearance in these subjects, although a possible effect of the *1D allele cannot be excluded in this study.


CONCLUSIONS
Although this study was performed using samples from a limited number of patients, routine genotyping of CYP1A2 *1F, *1C or *1D polymorphisms for their effect on metabolic capacity is, at least in Caucasians, not yet indicated.
Kootstra-Ros
Jenny E
JE
Department of Clinical Chemistry, St Jansdal Hospital, PO Box 138, 3840 AC Harderwijk, The Netherlands.
Smallegoor
Windy
W
van der Weide
Jan
J
D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics*; D003024:Clozapine / Q000097:blood / Q000493:pharmacokinetics*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D008657:Metabolic Clearance Rate / Q000235:genetics; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*; D012907:Smoking; D044465:White People / Q000235:genetics
D014150:Antipsychotic Agents; D019388:Cytochrome P-450 CYP1A2; D003024:Clozapine