Plasma clozapine concentration coefficients of variation in a long-term study

Francisco J. Diaz; Jose De Leon; Richard C. Josiassen; Thomas B. Cooper; George M. Simpson

doi:10.1016/j.schres.2004.03.017

Plasma clozapine concentration coefficients of variation in a long-term study

Francisco J. Diaz
, Jose De Leon
, Richard C. Josiassen
, Thomas B. Cooper
, George M. Simpson

Research output: Contribution to journal › Article › peer-review

54 Scopus citations

Abstract

Kurz et al. conducted the first study of the intra-individual variability of clozapine plasma concentrations but did not take into account the effect of smoking and co-medication. As patients were receiving varying doses, Kurz et al. standardized plasma levels by using a plasma level/dose/kg ratio. In 15 patients, the mean coefficient of variation (CV) was 53% (S.D.=21). In this new study, plasma clozapine and norclozapine concentrations were measured every 2 weeks in 47 patients randomized to 100, 300, or 600 mg/day for 16-week double-blind clozapine trials under controlled conditions (stable smoking, limited co-medication and absence of caffeinated beverages). For 100, 300 and 600 mg/day, the respective mean CVs for plasma clozapine concentrations were 23% (S.D.=14), 19% (S.D.=11) and 18% (S.D.=8). For the combined concentrations of clozapine and norclozapine, the respective mean CVs were 20% (S.D.=13), 16% (S.D.=9) and 15% (S.D.=7). Under 100 mg/day, the mean CV for clozapine concentrations was significantly higher for heavy smokers than non-heavy smokers (32%, S.D.=3 vs. 19%, S.D.=8) (p=0.03). Studies of CVs in other environments are needed. Clozapine CVs may be important in order to understand the importance of variations around the therapeutic range and to interpret drug interactions above the usual noise of measuring plasma concentrations.

Original language	English
Pages (from-to)	131-135
Number of pages	5
Journal	Schizophrenia Research
Volume	72
Issue number	2-3
DOIs	https://doi.org/10.1016/j.schres.2004.03.017
State	Published - Jan 1 2005

Bibliographical note

Funding Information:
This study was supported by the grant MH-47162 to George M. Simpson, MD and Richard C. Josiassen, PhD, from the US National Institute of Mental Health. The Novartis Research Institute provided free medication. The authors are grateful to Albert R. Di Dario, who was Superintendent of Norristown State Hospital at the time of this project and provided administrative support, and to Robert W. Ehlers, RN, for his consistent help with blood levels collection during this project.

Funding

This study was supported by the grant MH-47162 to George M. Simpson, MD and Richard C. Josiassen, PhD, from the US National Institute of Mental Health. The Novartis Research Institute provided free medication. The authors are grateful to Albert R. Di Dario, who was Superintendent of Norristown State Hospital at the time of this project and provided administrative support, and to Robert W. Ehlers, RN, for his consistent help with blood levels collection during this project.

Funders	Funder number
National Institute of Mental Health	R01MH047162

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Clozapine
Pharmacokinetics
Plasma clozapine concentrations

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

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10.1016/j.schres.2004.03.017

Cite this

@article{1e9089416deb4868ba3dc487c3963cec,

title = "Plasma clozapine concentration coefficients of variation in a long-term study",

abstract = "Kurz et al. conducted the first study of the intra-individual variability of clozapine plasma concentrations but did not take into account the effect of smoking and co-medication. As patients were receiving varying doses, Kurz et al. standardized plasma levels by using a plasma level/dose/kg ratio. In 15 patients, the mean coefficient of variation (CV) was 53\% (S.D.=21). In this new study, plasma clozapine and norclozapine concentrations were measured every 2 weeks in 47 patients randomized to 100, 300, or 600 mg/day for 16-week double-blind clozapine trials under controlled conditions (stable smoking, limited co-medication and absence of caffeinated beverages). For 100, 300 and 600 mg/day, the respective mean CVs for plasma clozapine concentrations were 23\% (S.D.=14), 19\% (S.D.=11) and 18\% (S.D.=8). For the combined concentrations of clozapine and norclozapine, the respective mean CVs were 20\% (S.D.=13), 16\% (S.D.=9) and 15\% (S.D.=7). Under 100 mg/day, the mean CV for clozapine concentrations was significantly higher for heavy smokers than non-heavy smokers (32\%, S.D.=3 vs. 19\%, S.D.=8) (p=0.03). Studies of CVs in other environments are needed. Clozapine CVs may be important in order to understand the importance of variations around the therapeutic range and to interpret drug interactions above the usual noise of measuring plasma concentrations.",

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author = "Diaz, \{Francisco J.\} and \{De Leon\}, Jose and Josiassen, \{Richard C.\} and Cooper, \{Thomas B.\} and Simpson, \{George M.\}",

note = "Funding Information: This study was supported by the grant MH-47162 to George M. Simpson, MD and Richard C. Josiassen, PhD, from the US National Institute of Mental Health. The Novartis Research Institute provided free medication. The authors are grateful to Albert R. Di Dario, who was Superintendent of Norristown State Hospital at the time of this project and provided administrative support, and to Robert W. Ehlers, RN, for his consistent help with blood levels collection during this project.",

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AU - Simpson, George M.

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AB - Kurz et al. conducted the first study of the intra-individual variability of clozapine plasma concentrations but did not take into account the effect of smoking and co-medication. As patients were receiving varying doses, Kurz et al. standardized plasma levels by using a plasma level/dose/kg ratio. In 15 patients, the mean coefficient of variation (CV) was 53% (S.D.=21). In this new study, plasma clozapine and norclozapine concentrations were measured every 2 weeks in 47 patients randomized to 100, 300, or 600 mg/day for 16-week double-blind clozapine trials under controlled conditions (stable smoking, limited co-medication and absence of caffeinated beverages). For 100, 300 and 600 mg/day, the respective mean CVs for plasma clozapine concentrations were 23% (S.D.=14), 19% (S.D.=11) and 18% (S.D.=8). For the combined concentrations of clozapine and norclozapine, the respective mean CVs were 20% (S.D.=13), 16% (S.D.=9) and 15% (S.D.=7). Under 100 mg/day, the mean CV for clozapine concentrations was significantly higher for heavy smokers than non-heavy smokers (32%, S.D.=3 vs. 19%, S.D.=8) (p=0.03). Studies of CVs in other environments are needed. Clozapine CVs may be important in order to understand the importance of variations around the therapeutic range and to interpret drug interactions above the usual noise of measuring plasma concentrations.

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KW - Pharmacokinetics

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M3 - Article

C2 - 15560958

AN - SCOPUS:9244244152

SN - 0920-9964

VL - 72

SP - 131

EP - 135

JO - Schizophrenia Research

JF - Schizophrenia Research

IS - 2-3

ER -

Plasma clozapine concentration coefficients of variation in a long-term study

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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