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Cytotoxicity and pharmacokinetics of cladribine metabolite, 2-chloroadenine in patients with leukemia
Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
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2004 (Engelska)Ingår i: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 210, nr 2, s. 171-177Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
2004. Vol. 210, nr 2, s. 171-177
Nyckelord [en]
leukemia, cladribine, metabolism, chloroadenine, pharmacokinetics
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-23411DOI: 10.1016/j.canlet.2004.03.007Lokalt ID: 2858OAI: oai:DiVA.org:liu-23411DiVA, id: diva2:243725
Tillgänglig från: 2009-10-07 Skapad: 2009-10-07 Senast uppdaterad: 2017-12-13

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Juliusson, Gunnar

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HälsouniversitetetOnkologiHematologiska kliniken US
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Cancer Letters
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