Influence of dose, gender, and cigarette smoking on clozapine plasma concentrations

Abstract

Introduction

Therapeutic drug monitoring (TDM) of clozapine is a very useful method for verifying both the correct intake and the interindividual variability of its metabolism, thereby avoiding the risk of toxicity. The purposes of this paper were to discover how many patients using clozapine in common clinical practice have clozapine plasma concentration (PC) levels in the proposed reference range and to identify factors that influence clozapine PC levels.

Methods

Our study included 100 inpatients (diagnosed with schizophrenia or schizoaffective disorder) taking standard doses of clozapine (100–700 mg/day). Clozapine concentration was measured by high-performance liquid chromatography. Correlations between doses and PC levels and the influence of smoking and gender on clozapine PC levels were calculated.

Results

A large number of the patients (67%) had PC levels outside the proposed reference range. The clozapine PC levels were influenced by dose, gender, and cigarette smoking.

Conclusion

The correlations between dose, gender, and cigarette smoking and clozapine PC levels highlighted by our study overlap other research. It was surprising to find such a large number of patients with clozapine PC levels outside the therapeutic range. This result suggests the importance of clozapine TDM due to misunderstood inter- and/or intraindividual variability or misestimated partial therapeutic compliance.

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Keywords:

• therapeutic drug monitoring
• plasma levels
• interindividual variability
• schizophrenia
• schizoaffective disorder

View correction statement:

Influence of dose, gender, and cigarette smoking on clozapine plasma concentrations [Corrigendum]

Acknowledgments

The authors thank Dr Balazova and Anne Johnson for proofreading the text. Dr Mayerova reports personal fees from the Ministry of Education, Youth and Sports of the Czech Republic, project CEITEC 2020 (LQ1601); grants from the Ministry of Health, Czech Republic, project for conceptual development of research organization 65269705 (University Hospital Brno, Czech Republic); and funds from a research grant from the Grant Agency of the Ministry of Health of the Czech Republic (AZV) 15-31063A, during the conduct of the study. Dr Ustohal reports personal fees from the Ministry of Education, Youth and Sports of the Czech Republic, project CEITEC 2020 (LQ1601) and grants from the Ministry of Health, Czech Republic, project for conceptual development of research organization 65269705 (University Hospital Brno, Czech Republic), during the conduct of the study.

Author contributions

MM: data sampling, study coordination, literature search, and manuscript editing. LU: data analysis, literature search, and manuscript editing. JJ: statistics gathering. JP: blood sample analysis. TK and EC: supervising and literature search. All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.