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Cytotoxicity and pharmacokinetics of cladribine metabolite, 2-chloroadenine in patients with leukemia
Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
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2004 (English)In: Cancer Letters, ISSN 0304-3835, Vol. 210, no 2, 171-177 p.Article in journal (Refereed) Published
Abstract [en]

The nucleoside analog 2-chlorodeoxyadenosine (Cladribine, CdA) is used in the treatment of patients with several hematological malignancies. After administration of CdA, the major catabolite measured in plasma and urine is 2-chloroadenine (CAde). This study was performed to determine the pharmacokinetics after oral and intravenous (iv) infusion of CdA in patients treated for chronic lymphocytic leukemia and to evaluate the toxicity of CAde to leukemia cells in vitro. CdA and CAde were also determined in plasma from 31 patients and in urine from 16 patients with reversed-phase high-performance liquid chromatographic. The toxicity of CdA and CAde was also determined in leukemic cells from 7 patients by fluorometric microculture cyotoxicity assay. Five times more CAde was quantified after oral treatment compared with an iv infusion of CdA. After iv infusion, the half-life was the same for CdA and CAde, but after oral administration the half-life was doubled for CAde. Excreted amount of CAde in urine constituted about 1.1% after iv infusion and 4.7% after oral CdA treatment. In vitro exposure of leukemia cells to CAde showed that it was eight times less toxic as compared to CdA. We conclude that CAde has a lower cytotoxic effect than CdA but may contribute significantly to the cytotoxicity after oral administration.

Place, publisher, year, edition, pages
2004. Vol. 210, no 2, 171-177 p.
Keyword [en]
leukemia, cladribine, metabolism, chloroadenine, pharmacokinetics
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-23411DOI: 10.1016/j.canlet.2004.03.007Local ID: 2858OAI: diva2:243725
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2011-01-12

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Juliusson, Gunnar
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Faculty of Health SciencesOncologyDepartment of Haematology UHL
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