| Item |
Information |
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Drug Groups
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approved; investigational |
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Description
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An antineoplastic agent used in the treatment of lymphoproliferative diseases including hairy-cell leukemia. [PubChem] |
| Indication |
For the treatment of active hairy cell leukemia (leukemic reticuloendotheliosis) as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms. Also used as an alternative agent for the treatment of chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin's lymphoma, and cutaneous T-cell lymphoma. |
| Pharmacology |
Cladribine is a synthetic purine nucleoside that acts as an antineoplastic agent with immunosuppressive effects. Cladribine differs structurally from deoxyadenosine only by the presence of a chlorine atom at position 2 of the purine ring, which results in resistance to enzymatic degradation by adenosine deaminase. Due to this resistance, cladribine exhibits a more prolonged cytotoxic effect than deoxyadenosine against resting and proliferating lymphocytes. Cladribine is one of a group of chemotherapy drugs known as the anti-metabolites. Anti-metabolites stop cells from making and repairing DNA, which are processes that are necessary for cancer cells to grow and multiply. |
| Toxicity |
Symptoms of overdose include irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia and thrombocytopenia. |
| Affected Organisms |
| • |
Humans and other mammals |
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| Biotransformation |
Metabolized in all cells with deoxycytidine kinase activity to 2-chloro-2'-deoxyadenosine-5'-triphosphate |
| Absorption |
Oral bioavailability is 34 to 48%. |
| Half Life |
5.4 hours |
| Protein Binding |
20% |
| Distribution |
* 4.5 ± 2.8 L/kg [patients with hematologic malignancies]
* 9 L/kg |
| Clearance |
* 978 +/- 422 mL/h/kg |
| References |
| • |
Warnke C, Wiendl H, Hartung HP, Stuve O, Kieseier BC: Identification of targets and new developments in the treatment of multiple sclerosis - focus on cladribine. Drug Des Devel Ther. 2010 Jul 21;4:117-26.
[Pubmed]
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| • |
Sigal DS, Miller HJ, Schram ED, Saven A: Beyond hairy cell: the activity of cladribine in other hematologic malignancies. Blood. 2010 Jul 15.
[Pubmed]
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| • |
Khalid BA, Hamilton NT, Cauchi MN: Binding of thyroid microsomes by lymphocytes from patients with thyroid disease and normal subjects. Clin Exp Immunol. 1976 Jan;23(1):28-32.
[Pubmed]
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| • |
Sampat K, Kantarjian H, Borthakur G: Clofarabine: emerging role in leukemias. Expert Opin Investig Drugs. 2009 Oct;18(10):1559-64.
[Pubmed]
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Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S: Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
[Pubmed]
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Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. Epub 2009 Jul 1.
[Pubmed]
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| • |
Larson ML, Venugopal P: Clofarabine: a new treatment option for patients with acute myeloid leukemia. Expert Opin Pharmacother. 2009 Jun;10(8):1353-7.
[Pubmed]
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