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

Mong Liang Lu, Chun Hsin Chen, Pei Ting Kuo, Chia Hui Lin, Tzu Hua Wu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 ≧22.77ng/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 >5.63ng/mL and DMO C/D ratio>0.35ng/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.

Original languageEnglish
Pages (from-to)139-145
JournalSchizophrenia Research
Volume193
DOIs
Publication statusPublished - Mar 2018

Fingerprint

olanzapine
Schizophrenia
Drug Monitoring
C-Peptide
Waist Circumference
desmethylolanzapine
Fasting
Body Mass Index
Therapeutics
Cholesterol
High Pressure Liquid Chromatography

Keywords

  • Metabolic syndrome
  • N-desmethy-olanzapine
  • Olanzapine
  • Schizophrenia
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

@article{d47a91f575224270ae1f39776ddfbc73,
title = "Application of plasma levels of olanzapine and N-desmethyl-olanzapine to monitor metabolic parameters in patients with schizophrenia",
abstract = "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 ≧22.77ng/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 >5.63ng/mL and DMO C/D ratio>0.35ng/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.",
keywords = "Metabolic syndrome, N-desmethy-olanzapine, Olanzapine, Schizophrenia, Therapeutic drug monitoring",
author = "Lu, {Mong Liang} and Chen, {Chun Hsin} and Kuo, {Pei Ting} and Lin, {Chia Hui} and Wu, {Tzu Hua}",
year = "2018",
month = "3",
doi = "10.1016/j.schres.2017.07.022",
language = "English",
volume = "193",
pages = "139--145",
journal = "Schizophrenia Research",
issn = "0920-9964",
publisher = "Elsevier",

}

TY - JOUR

T1 - Application of plasma levels of olanzapine and N-desmethyl-olanzapine to monitor metabolic parameters in patients with schizophrenia

AU - Lu, Mong Liang

AU - Chen, Chun Hsin

AU - Kuo, Pei Ting

AU - Lin, Chia Hui

AU - Wu, Tzu Hua

PY - 2018/3

Y1 - 2018/3

N2 - 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 ≧22.77ng/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 >5.63ng/mL and DMO C/D ratio>0.35ng/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.

AB - 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 ≧22.77ng/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 >5.63ng/mL and DMO C/D ratio>0.35ng/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.

KW - Metabolic syndrome

KW - N-desmethy-olanzapine

KW - Olanzapine

KW - Schizophrenia

KW - Therapeutic drug monitoring

UR - http://www.scopus.com/inward/record.url?scp=85023648299&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85023648299&partnerID=8YFLogxK

U2 - 10.1016/j.schres.2017.07.022

DO - 10.1016/j.schres.2017.07.022

M3 - Article

VL - 193

SP - 139

EP - 145

JO - Schizophrenia Research

JF - Schizophrenia Research

SN - 0920-9964

ER -