The Association Between Clozapine Plasma Concentration, CYP2D6 (*10, *2) Polymorphisms and Risk of Adverse Reactions.

Abstract

Background: The aim of this article was to study the relationships between the risk of adverse reactions, plasma concentration, and cytochrome P450 2D6 rs1065852 (*10) and rs16947 (*2) polymorphisms for clozapine.

Methods: The steady-state clozapine plasma concentration of 100 Chinese inpatients with schizophrenia was determined using 2-dimensional liquid chromatography. The polymorphisms of cytochrome P450 2D6 (*10 and *2) were determined using fluorescent in situ hybridization protocols.

Results: The decreased percentages of white blood cells and neutrophils and the elevated percentages of creatine kinase, alanine aminotransferase, and aspartate transferase in patients treated with clozapine for 6 months were linearly associated with clozapine plasma concentration. Compared with the corresponding groups, the clozapine plasma concentrations of individuals with the *10TT genotype and individuals with the *2CC genotype were the highest (P < .05). The decreased percentages of white blood cells and neutrophils and elevated percentages of creatine kinase, alanine aminotransferase, and aspartate transferase for patients with the *10TT genotype were significantly higher than those for patients with the *10CC and *10CT genotypes (P < .05). The decreased percentages of white blood cells and neutrophils and increased percentages of creatine kinase, alanine aminotransferase, and aspartate transferase for patients with the *2CC genotype were significantly higher than those of the other groups (P < .05). The therapeutic reference range of clozapine for Chinese patients with schizophrenia was defined as 102.5-483.1 ng/mL.

Conclusion: This study demonstrated that the determination of cytochrome P450 2D6 polymorphisms and therapeutic drug monitoring of clozapine might be beneficial for identifying patients with a higher risk of adverse reactions.