Relationship Between Plasma Olanzapine and N-Desmethyl-Olanzapine Concentration and Metabolic Parameters in Patients With Schizophrenia

OBJECTIVES: The aim of the present study was to investigate a potential relationship between metabolic parameters and steady-state plasma concentrations of olanzapine (OLA) and its metabolite, 4-N'-desmethyl-olanzapine (DMO) in patients with schizophrenia taking therapeutic doses. METHODS: A total of 352 inpatients, diagnosed with schizophrenia according to the DSM-V criteria and treated with OLA, were investigated. The plasma concentrations of OLA and DMO were measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Fasting blood samples were measured for insulin, glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), C-reactive protein (CRP) and homocysteine, and differences in these parameters were investigated in relation to plasma concentrations of OLA and DMO. RESULTS: Lower plasma DMO concentrations were associated with higher glucose and TG levels and homeostasis model assessment of insulin resistance (HOMA-IR), while higher plasma OLA concentrations were associated with higher CRP and homocysteine levels in the OLA-treated patients with schizophrenia. CONCLUSION: These results demonstrate that OLA and its metabolite DMO may have different effects on OLA-induced metabolic abnormalities. DMO might have a counteracting effects on glucose-insulin homeostasis and lipid metabolic abnormalities, which suggests that regular measure of various metabolic parameters and drug monitoring on both OLA and DMO are recommended in OLA-treated patients with schizophrenia.