Assessment of Genetic and Lifestyle Factors on Clozapine and N-desmethylclozapine Plasma Levels in Schizophrenia Patients

Plasma concentrations of clozapine (CLZ) vary due to several factors, including age, sex, smoking habits, caffeine consumption, and comedication. Genetic variations might also explain the variations for plasma CLZ (2). Among genetic polymorphisms that may have a role in CLZ metabolism, CYP1A2*1F is a strong candidate.. Cytochrome P450 oxidoreductase (POR) gene POR*28 variation is also potentially a considerable target.

Within this context, we have investigated the influence of genetic (CYP1A2*1F and POR*28) polymorphisms and non-genetic factors (caffeine consumption and cigarette smoking) on CLZ and main metabolite DCLZ concentrations. For this purpose, 112 schizophrenia patients receiving CLZ were included in the current study. Plasma CLZ and N-desmethylclozapine (DCLZ) levels were analysed by using HPLC-UV detector set at 220 nm. Genetic variations were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.

There was no significant difference between the genotype groups on CLZ, DCLZ levels, and DCLZ/CLZ ratios. In the subgroups created according to the patient’s CYP1A2 genotype, and smoking and caffeine consumption status, significant differences have been observed between POR*28 wild-type and variant genotype groups. Regression model analyses revealed that the POR*28 polymorphism correlates significantly with both CLZ and DLCZ (ng/ml/mg/kg) levels.

The outcome of our investigation findings suggests that, considering both genetic and non-genetic factors may have the potential to increase efficacy and decrease adverse drug reactions in the treatment of schizophrenia with CLZ.

Publikationsverlauf

Artikel online veröffentlicht:
12. März 2024