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

doi:10.1371/journal.pone.0148539

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 journal › Article › peer-review

21 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 (C_OLZ) and DMO (C_DMO) in schizophrenic patients 12 hours post-dose were assessed. The correlations of C_OLZ and C_DMO 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 C_OLZ and C_OLZ/C_DMO ratio for maintenance of satisfactory efficacy. Results: A total of 151 samples from patients with schizophrenia were analyzed for individual C_OLZ and C_DMO levels. The mean C_OLZ and C_DMO levels were 37.0 ± 25.6 and 6.9 ± 4.7 ng/mL, respectively, and C_OLZ was ~50% higher in female or nonsmokers (pOLZ and C_DMO. Linear relationships between C_OLZ and OLZ dose were observed in both nonsmokers and smokers (r_s = 0.306, 0.426, pDMO was only correlated with OLZ dose in smokers (r_s = 0.485, pOLZ was marginally negatively correlated with the total PANSS score. The total PANSS score was significantly negatively correlated with the C_OLZ/C_DMO ratio (pOLZ/C_DMO ratio ≥2.99 or C_OLZ ≥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 C_OLZ/C_DMO 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 language	English
Article number	e0148539
Journal	PLoS ONE
Volume	11
Issue number	2
DOIs	https://doi.org/10.1371/journal.pone.0148539
Publication status	Published - Feb 1 2016

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@article{11d7785d9ae441ee9eb5a85628c6baf4,

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

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.",

author = "Lu, {Mong Liang} and Wu, {Yi Xiu} and Chen, {Chun Hsin} and Kuo, {Pei Ting} and Chen, {Yi Hua} and Lin, {Chia Hui} and Wu, {Tzu Hua}",

note = "Publisher Copyright: {\textcopyright} 2016 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2016",

month = feb,

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doi = "10.1371/journal.pone.0148539",

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

AU - Lu, Mong Liang

AU - Wu, Yi Xiu

AU - Chen, Chun Hsin

AU - Kuo, Pei Ting

AU - Chen, Yi Hua

AU - Lin, Chia Hui

AU - Wu, Tzu Hua

N1 - Publisher Copyright: © 2016 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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.

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

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