Application of plasma levels of olanzapine and N-desmethyl-olanzapine to monitor metabolic parameters in patients with schizophrenia

Metabolic disturbance is a common side effect of olanzapine (OLZ); however, the relationships between plasma OLZ concentration (COLZ) and metabolic disturbance remain unclear. Our previous study revealed that COLZ ≧ 22.77 ng/mL was a positive predictor of therapeutic efficacy in patients with schizophrenia. This study aimed to investigate the roles of OLZ or N-desmethyl-olanzapine (DMO) in metabolic outcomes among OLZ-treated patients with schizophrenia. The metabolic syndrome (MS) was diagnosed based on the modified the National Cholesterol Education Program Adult Treatment Panel III criteria for Asians. HPLC-ECD analytical system was applied to determine the COLZ and DMO concentration (CDMO). The absolute drug levels and concentration-to-dose ratios (C/D ratios) were tested for their correlations to metabolic parameters. Total 151 fasting blood samples from patients with schizophrenia were collected. DMO C/D ratio negatively correlated with weight, body mass index, waist circumference, and C-peptide level. The receiver operator characteristic analysis determined a threshold CDMO > 5.63 ng/mL and DMO C/D ratio > 0.35 ng/mL/mg were negative predictors of MS. The COLZ/CDMO ratio > 6.03 was identified as positive predictor of MS. Combined with previous study result, we proposed that the optimal OLZ treatment should maintain COLZ/CDMO ratio between 3 and 6 to maximize the clinical efficacy and minimize the metabolic side effects. Our findings suggested that therapeutic drug monitoring on OLZ and DMO is a valuable tool to monitor metabolic side effects in OLZ-treated patients with schizophrenia.