Application of plasma levels of olanzapine and N-desmethyl-olanzapine to monitor clinical efficacy in patients with schizophrenia

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: This therapeutic drug monitoring (TDM) study aimed to determine the role of olanzapine (OLZ) and N-desmethyl-OLZ (DMO) levels in the therapeutic efficacy of OLZ in patients with schizophrenia. Method: Plasma concentrations of OLZ (COLZ) and DMO (CDMO) in schizophrenic patients 12 hours post-dose were assessed. The correlations of COLZ and CDMO with the various scores of the Positive and Negative Syndrome Scale (PANSS) were evaluated. A receiver operating characteristic curve (ROC) was utilized to identify the threshold COLZ and COLZ/CDMO ratio for maintenance of satisfactory efficacy. Results: A total of 151 samples from patients with schizophrenia were analyzed for individual COLZ and CDMO levels. The mean COLZ and CDMO levels were 37.0 ± 25.6 and 6.9 ± 4.7 ng/mL, respectively, and COLZ was ~50% higher in female or nonsmokers (pOLZ and CDMO. Linear relationships between COLZ and OLZ dose were observed in both nonsmokers and smokers (rs = 0.306, 0.426, pDMO was only correlated with OLZ dose in smokers (rs = 0.485, pOLZ was marginally negatively correlated with the total PANSS score. The total PANSS score was significantly negatively correlated with the COLZ/CDMO ratio (pOLZ/CDMO ratio ≥2.99 or COLZ ≥22.77 ng/mL as a predictor of maintenance of an at least mildly ill status (PANSS score ≤58) of schizophrenia in all patients. Conclusions: A significantly negative correlation between the steady-state COLZ/CDMO ratio and total PANSS score was observed in Taiwanese schizophrenic patients. TDM of both OLZ and DMO levels could assist clinical practice when individualizing OLZ dosage adjustments for patients with schizophrenia.

Original languageEnglish
Article numbere0148539
JournalPLoS One
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

Fingerprint

olanzapine
Schizophrenia
Plasmas
monitoring
dosage
Drug Monitoring
therapeutics
drugs
Maintenance
Monitoring
Pharmaceutical Preparations
desmethylolanzapine
schizophrenia
ROC Curve

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Application of plasma levels of olanzapine and N-desmethyl-olanzapine to monitor clinical efficacy in patients with schizophrenia. / Lu, Mong Liang; Wu, Yi Xiu; Chen, Chun Hsin; Kuo, Pei Ting; Chen, Yi Hua; Lin, Chia Hui; Wu, Tzu Hua.

In: PLoS One, Vol. 11, No. 2, e0148539, 01.02.2016.

Research output: Contribution to journalArticle

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abstract = "Background: This therapeutic drug monitoring (TDM) study aimed to determine the role of olanzapine (OLZ) and N-desmethyl-OLZ (DMO) levels in the therapeutic efficacy of OLZ in patients with schizophrenia. Method: Plasma concentrations of OLZ (COLZ) and DMO (CDMO) in schizophrenic patients 12 hours post-dose were assessed. The correlations of COLZ and CDMO with the various scores of the Positive and Negative Syndrome Scale (PANSS) were evaluated. A receiver operating characteristic curve (ROC) was utilized to identify the threshold COLZ and COLZ/CDMO ratio for maintenance of satisfactory efficacy. Results: A total of 151 samples from patients with schizophrenia were analyzed for individual COLZ and CDMO levels. The mean COLZ and CDMO levels were 37.0 ± 25.6 and 6.9 ± 4.7 ng/mL, respectively, and COLZ was ~50{\%} higher in female or nonsmokers (pOLZ and CDMO. Linear relationships between COLZ and OLZ dose were observed in both nonsmokers and smokers (rs = 0.306, 0.426, pDMO was only correlated with OLZ dose in smokers (rs = 0.485, pOLZ was marginally negatively correlated with the total PANSS score. The total PANSS score was significantly negatively correlated with the COLZ/CDMO ratio (pOLZ/CDMO ratio ≥2.99 or COLZ ≥22.77 ng/mL as a predictor of maintenance of an at least mildly ill status (PANSS score ≤58) of schizophrenia in all patients. Conclusions: A significantly negative correlation between the steady-state COLZ/CDMO ratio and total PANSS score was observed in Taiwanese schizophrenic patients. TDM of both OLZ and DMO levels could assist clinical practice when individualizing OLZ dosage adjustments for patients with schizophrenia.",
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AU - Lin, Chia Hui

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AB - Background: This therapeutic drug monitoring (TDM) study aimed to determine the role of olanzapine (OLZ) and N-desmethyl-OLZ (DMO) levels in the therapeutic efficacy of OLZ in patients with schizophrenia. Method: Plasma concentrations of OLZ (COLZ) and DMO (CDMO) in schizophrenic patients 12 hours post-dose were assessed. The correlations of COLZ and CDMO with the various scores of the Positive and Negative Syndrome Scale (PANSS) were evaluated. A receiver operating characteristic curve (ROC) was utilized to identify the threshold COLZ and COLZ/CDMO ratio for maintenance of satisfactory efficacy. Results: A total of 151 samples from patients with schizophrenia were analyzed for individual COLZ and CDMO levels. The mean COLZ and CDMO levels were 37.0 ± 25.6 and 6.9 ± 4.7 ng/mL, respectively, and COLZ was ~50% higher in female or nonsmokers (pOLZ and CDMO. Linear relationships between COLZ and OLZ dose were observed in both nonsmokers and smokers (rs = 0.306, 0.426, pDMO was only correlated with OLZ dose in smokers (rs = 0.485, pOLZ was marginally negatively correlated with the total PANSS score. The total PANSS score was significantly negatively correlated with the COLZ/CDMO ratio (pOLZ/CDMO ratio ≥2.99 or COLZ ≥22.77 ng/mL as a predictor of maintenance of an at least mildly ill status (PANSS score ≤58) of schizophrenia in all patients. Conclusions: A significantly negative correlation between the steady-state COLZ/CDMO ratio and total PANSS score was observed in Taiwanese schizophrenic patients. TDM of both OLZ and DMO levels could assist clinical practice when individualizing OLZ dosage adjustments for patients with schizophrenia.

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