Biological variation in clozapine and metabolite reporting during therapeutic drug monitoring

Pasindu Wickramarachchi; Jessica M Boyd; Dennis J Orton

doi:10.1016/j.cca.2022.04.005

Biological variation in clozapine and metabolite reporting during therapeutic drug monitoring

Clin Chim Acta. 2022 Jun 1:531:183-187. doi: 10.1016/j.cca.2022.04.005. Epub 2022 Apr 8.

Authors

Pasindu Wickramarachchi¹, Jessica M Boyd², Dennis J Orton³

Affiliations

¹ Department of Neuroscience, University of Calgary, Calgary, AB, Canada.
² Department of Pathology & Laboratory Medicine, Cumming School of Medicine, University of Calgary and Alberta Precision Laboratories, AB, Canada.
³ Department of Pathology & Laboratory Medicine, Cumming School of Medicine, University of Calgary and Alberta Precision Laboratories, AB, Canada. Electronic address: dennis.orton@ucalgary.ca.

PMID: 35398248
DOI: 10.1016/j.cca.2022.04.005

Abstract

Background: Clozapine (CLO) is an atypical antipsychotic used in management of treatment-resistant schizophrenia. Adverse drug reactions are caused by both CLO and its primary metabolite, norclozapine (NCLO). We defined the biological variability of CLO, NCLO, and the CLO to NCLO ratio (CNR) as well as assess the impact of reporting CLO and NCLO routinely.

Methods: The CV_i and CV_g were calculated from 1904 results from 247 patients by CV-ANOVA, and ANOVA, respectively, for CLO, NCLO, and the CNR. Association between each were also analyzed against a number of parameters including age and gender, complete blood count (CBC), kidney and liver function tests, lipids, and glucose within 24 h of CLO measurement.

Results: For CLO, NCLO and CNR, the CV_i was calculated as 19.3%, 19.2%, and 14.7%, and the CV_g was 46.9%, 51.4%, and 36.3%, respectively. A total of 87 patients (19.7%) demonstrated higher NCLO results than CLO, with a ratio as low as 0.47. Kidney function was also found to have a statistically significant relationship to CLO and NCLO levels.

Conclusions: We provide data for biological variability of CLO metabolism as well as while providing some evidence for reporting NCLO values clinically.

Keywords: Adverse drug reactions; Analytical quality targets; Biological variation; Clozapine; Norclozapine; Therapeutic drug monitoring.

MeSH terms

Antipsychotic Agents* / adverse effects
Clozapine* / adverse effects
Drug Monitoring / methods
Humans
Schizophrenia* / drug therapy
Smoking

Substances

Antipsychotic Agents
Clozapine