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Pharmacopsychiatry 2006; 39(1): 20-22
DOI: 10.1055/s-2006-931475
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

In Vitro Toxicity of Clozapine, Olanzapine, and Quetiapine on Granulocyte-Macrophage Progenitors (GM-CFU)

A. Pessina1 , E. Turlizzi1 , A. Bonomi1 , F. Guizzardi1 , L. Cavicchini1 , C. Croera2 , S. Bareggi3
  • 1Institute of Microbiology, University of Milan, Italy
  • 2ECVAM, Institute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra, Italy
  • 3Department of Pharmacology, University of Milan, Italy
Further Information

Publication History

Received: 30.3.2005 Revised: 6.7.2005

Accepted: 31.8.2005

Publication Date:
02 February 2006 (online)

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In Vitro Toxicity of Clozapine, Olanzapine, and Quetiapine on Granulocyte-Macrophage Progenitors (GM-CFU)Pharmacopsychiatry 2006; 39(04): 160-160
DOI: 10.1055/s-2006-947212

Introduction: Atypical antipsychotics may lead to agranulocytosis because of the apoptosis caused by cells binding nitrenium molecules. Studies showing the direct myelotoxicity of clozapine were undertaken years ago using different assays, and thus it is difficult to compare them with those of clozapine’s analogues that have been more recently reported as causing neutropenia, agranulocytosis, and thrombocytopenia. Methods: We compared the direct toxicity of clozapine, olanzapine, quetiapine, and chlorpromazine using a previously standardized GM-CFU assay validated for predicting neutropenia. Results: The results showed that all of the drugs were characterized by dose-dependent toxicity, which was greatest in the case of chlorpromazine (IC90 = 10.02 ± 0.69 μg/mL), followed by olanzapine (IC90 = 13.43 ± 1.23 μg/mL), clozapine (IC90 = 44.71 ± 4.42 μg/mL), and quetiapine (IC90 = 137.24 ± 15.36 μg/mL). Discussion: These data agree with recent clinical reports concerning the direct or mediated toxic effects of olanzapine on progenitor and committed cells (GM-CFU) and suggest that the correlation between its plasma levels and clinical effects warrants further investigation. There are no published data concerning the bone marrow pharmacokinetics of atypical antipsychotics or their possible bioactivation by the bone marrow cell compartment, but our findings suggest that they may affect hematopoiesis in different ways, such as the direct action of them or their metabolites due to bioactivation by hematopoietic cells themselves.

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Dr. Augusto Pessina

University of Milan

Institute of Microbiology

Via Pascal 36

20133 Milano

Italy

Phone: +39 02 250315072

Fax: +39 02 50315068

Email: augusto.pessina@unimi.it