Effect of Genetic Variants, Gender, and Co-treatment on Olanzapine Plasma Concentration in Chinese patients with schizophrenia

Abstract

Purpose Given the inter-individual variability in dose-corrected concentrations observed in olanzapine used, this study aimed to find factors that may have contributed to the variation in patients.Methods The trough plasma concentrations of olanzapine were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). All the patients enrolled were on steady olanzapine doses for at least two weeks. Our study simultaneously investigated the association of gender, co-treatment, kidney function, body weight, and UGT1A4, UGT2B7, UGT2B15, CYP1A2, CYP2D6 variants on olanzapine dose-corrected concentrations (C/DOLZ) in 117 Chinese patients with schizophrenia.Results Multiple linear regression analyses suggested that gender, co-treatment with sodium valproate, and UGT1A4 variants had significantly affected C/DOLZ in inpatients with schizophrenia (P༜0.05). Females showed higher C/DOLZ levels compared to males, co-treatment with VPA exhibited lower C/DOLZ levels, UGT1A4 variants showed its significance (P = 0.005) in the multiple linear regression,Conclusions The results revealed that gender, co-treatment with VPA, and UGT1A4 variants significantly influenced C/DOLZ levels. This study provided some combined effects, especially genotype and co-treatment information, for clinicians to remind them when prescribing OLZ. The variability of C/DOLZ levels suggests that TDM could be a helpful tool in addition to a thorough clinical follow-up.