Dried blood spot analysis for therapeutic drug monitoring of Clozapine

Lisanne M. Geers, Dan Cohen, Laura M. Wehkamp, Kai Van Hateren, Remco A. Koster, Olga Yu Fedorenko, Arkadyi V. Semke, Nikolay Bokhan, Svetlana A. Ivanova, Jos G.W. Kosterink, Anton J.M. Loonen, Daan J. Touw

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Schizophrenia is a psychiatric disorder that affects approximately 0.4%–1% of the population worldwide. Diagnosis of schizophrenia is based primarily on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Clozapine is an antipsychotic drug that is mainly used in the treatment of schizophrenia patients who are refractory or intolerant to at least 2 other antipsychotics. Due to the high variability in pharmacokinetics of clozapine, therapeutic drug monitoring (TDM) is highly recommended for clozapine therapy. Objective: To develop and clinically validate a novel sampling method using dried blood spot (DBS) to support TDM of clozapine and norclozapine. Methods: From June 2014 to September 2014, 15 schizophrenia patients (18–55 years) treated with clozapine were included. Plasma, DBS samples made from venous samples (VDBS), and finger prick DBS (DBS) samples were obtained before administration and 2, 4, 6, and 8 hours after clozapine intake. The study was repeated in 6 Russian patients for external validation. Passing-Bablok regression and Bland-Altman analysis were used to compare the DBS, VDBS, and plasma results for clozapine and norclozapine. Results: The DBS validation results showed good linearity over the concentration time curve measured for clozapine and norclozapine. The accuracy and between- and within-day precision variation values were within accepted ranges. Different blood spot volumes and hematocrit values had no significant influence on the results. The DBS samples were stable at 20°C and 37°C for 2 weeks and at −20°C for 2 years. The mean clozapine and norclozapine DBS/plasma ratios were, respectively, 0.80 (95% CI, 0.76 to 0.85) and 1.063 (95% CI, 1.027 to 1.099) in Dutch patients. The mean clozapine DBS/DPS ratio in Russian patients was 0.70 (95% CI, 0.64 to 0.76). Conclusion: DBS analysis is a reliable tool for blood sampling and performing TDM of clozapine and norclozapine in daily practice and substantially extends the opportunities for TDM of clozapine.

Original languageEnglish
Pages (from-to)e1211-e1218
JournalJournal of Clinical Psychiatry
Volume78
Issue number9
DOIs
Publication statusPublished - 1 Nov 2017

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Dried Blood Spot Testing
Drug Monitoring
Clozapine
norclozapine
Schizophrenia
Antipsychotic Agents
Blood Volume

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Geers, L. M., Cohen, D., Wehkamp, L. M., Van Hateren, K., Koster, R. A., Fedorenko, O. Y., ... Touw, D. J. (2017). Dried blood spot analysis for therapeutic drug monitoring of Clozapine. Journal of Clinical Psychiatry, 78(9), e1211-e1218. https://doi.org/10.4088/JCP.16m11164

Dried blood spot analysis for therapeutic drug monitoring of Clozapine. / Geers, Lisanne M.; Cohen, Dan; Wehkamp, Laura M.; Van Hateren, Kai; Koster, Remco A.; Fedorenko, Olga Yu; Semke, Arkadyi V.; Bokhan, Nikolay; Ivanova, Svetlana A.; Kosterink, Jos G.W.; Loonen, Anton J.M.; Touw, Daan J.

In: Journal of Clinical Psychiatry, Vol. 78, No. 9, 01.11.2017, p. e1211-e1218.

Research output: Contribution to journalArticle

Geers, LM, Cohen, D, Wehkamp, LM, Van Hateren, K, Koster, RA, Fedorenko, OY, Semke, AV, Bokhan, N, Ivanova, SA, Kosterink, JGW, Loonen, AJM & Touw, DJ 2017, 'Dried blood spot analysis for therapeutic drug monitoring of Clozapine', Journal of Clinical Psychiatry, vol. 78, no. 9, pp. e1211-e1218. https://doi.org/10.4088/JCP.16m11164
Geers, Lisanne M. ; Cohen, Dan ; Wehkamp, Laura M. ; Van Hateren, Kai ; Koster, Remco A. ; Fedorenko, Olga Yu ; Semke, Arkadyi V. ; Bokhan, Nikolay ; Ivanova, Svetlana A. ; Kosterink, Jos G.W. ; Loonen, Anton J.M. ; Touw, Daan J. / Dried blood spot analysis for therapeutic drug monitoring of Clozapine. In: Journal of Clinical Psychiatry. 2017 ; Vol. 78, No. 9. pp. e1211-e1218.
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AU - Koster, Remco A.

AU - Fedorenko, Olga Yu

AU - Semke, Arkadyi V.

AU - Bokhan, Nikolay

AU - Ivanova, Svetlana A.

AU - Kosterink, Jos G.W.

AU - Loonen, Anton J.M.

AU - Touw, Daan J.

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