Interindividual variability in olanzapine steady-state concentrations in Chinese: exploring single nucleotide polymorphisms of metabolic enzymes.

Abstract

Aims: Olanzapine steady-state concentration can vary due to several factors. This study explores how physiological factors, smoking status, inflammation status, concomitant medications and metabolic enzyme single nucleotide polymorphisms (SNPs) influence its metabolic levels, aiming to guide personalized dosing.

Methods: This study analysed data from 310 olanzapine-treated patients at Beijing Anding Hospital. Liquid chromatography-mass spectrometry quantified 1002 serum concentrations. Eleven SNPs from CYP1A2, CYP3A5, UGT1A4 and FMO1/3 were identified through real-time fluorescence quantitative polymerase chain reaction. A Bayesian network was applied to elucidate causal relationships between variables, followed by g-computation to quantify the effect of individual factors on the dose-adjusted concentration (C/D ratio) of olanzapine. The Wilcoxon signed-rank test assessed the intraindividual variations in the steady-state C/D ratio.

Results: The Bayesian network suggested causality between smoking, sex, sertraline, Danggui-Longhui, valproic acid and the olanzapine C/D ratio. None of the SNPs reached significance levels. The Wilcoxon signed-rank test confirmed that both polypharmacy and inflammation increased the C/D ratio within individuals. G-computation showed that the olanzapine C/D ratio decreased by 1.135 in males and 0.821 with smoking. Danggui-Longhui, sertraline and valproic acid reduced the ratio by 1.134, 0.92427 and 0.832, respectively.

Conclusion: Our study confirms that sex, age, smoking, inflammation and coprescription with sertraline, Danggui-Longhui and valproic acid contributed to variability in olanzapine's steady-state concentration. Considering these factors in clinical practice may help to personalize olanzapine treatment in Asian patients.