Cigarette smoking has a differential effect on the plasma level of clozapine in Taiwanese schizophrenic patients associated with the CYP1A2 gene −163A/C single nucleotide polymorphism

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Abstract

Objective

The efficacy of clozapine clearance has been shown to be associated with smoking and genetic polymorphism of CYP1A2. This study aims to investigate the effect of smoking on the plasma level of clozapine in Taiwanese schizophrenic patients and its relevance to the CYP1A2 gene −163A/C single nucleotide polymorphism.

Materials and methods

A total of 143 hospitalized schizophrenic patients who had received clozapine therapy for at least 14 days were enrolled in this study. The trough plasma concentration of clozapine was measured with LC/MS/MS. The −163A/C variant in the CYP1A2 gene was identified by DNA sequencing and restriction fragment length polymorphism analysis. The effect of smoking on the clozapine level was examined by multiple linear regression analysis and its relation to the −163A/C variant of the CYP1A2 gene was analyzed using a general linear model with Bonferroni correction.

Results

Patients with smoking habits showed a significantly lower plasma level of clozapine than those without smoking habits (P=0.022) and the difference in clozapine levels between smokers and nonsmokers appeared to be significant in the individuals carrying the homozygous −163A allele (P=0.02). It was also found that nonsmokers carrying the −163A allele tended to have higher plasma levels of clozapine. This tendency was not found in the individuals with smoking habits.

Conclusion

Cigarette smoking has a significant impact on the plasma level of clozapine in Taiwanese schizophrenic patients carrying the homozygous −163A allele in the CYP1A2 gene. Cigarette smoking may increase the clearance of clozapine in these patients.

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