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Trade names | Leustatin, Mavenclad, others[1] |
Other names | 2-Chlorodeoxyadenosine; 2-Chloro-2'-deoxyadenosine; 2-CdA |
AHFS/Drugs.com | Monograph |
MedlinePlus | a693015 |
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Routes of administration | Intravenous, subcutaneous (liquid), by mouth (tablet) |
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Pharmacokinetic data | |
Bioavailability | 100% (i.v.); 37 to 51% (orally)[5] |
Protein binding | 25% (range 5-50%);[6] up to 20% (orally) [7] |
Metabolism | Mostly via intracellular kinases; 15-18% is excreted unchanged.[6]
Intravenous and subcutaneous bolus injection: 15-18% is excreted unchanged After oral administration, 25% (±21%) of dose is excreted unchanged in urine and 3.8% as a metabolite.[7] |
Elimination half-life | Approximately 10 hours after both intravenous infusion and subcutaneous bolus injection ranging from 5.6 to 7.6 hours[6] and 18.4 to 19.7 hours after oral administration, indicative of different elimination phases. |
Excretion | Urinary[6] |
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ECHA InfoCard | 100.164.726 |
Chemical and physical data | |
Formula | C10H12ClN5O3 |
Molar mass | 285.69 g·mol−1 |
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Cladribine, sold under the brand name Leustatin, among others, is a medication used to treat hairy cell leukemia (leukemic reticuloendotheliosis) and B-cell chronic lymphocytic leukemia.[8][9] Cladribine, sold under the brand name Mavenclad, is used for the treatment of adults with highly active forms of relapsing-remitting multiple sclerosis.[10]
Cladribine is a purine analogue that selectively targets and suppresses lymphocytes implicated in the underlying pathogenesis of multiple sclerosis and B-cell leukaemia.[11][7][12] Chemically, it mimics the nucleoside deoxyadenosine. However, unlike deoxyadenosine, it is relatively resistant to breakdown by the enzyme adenosine deaminase, which causes it to accumulate in targeted cells and interfere with the cell's ability to process DNA.[7] Cladribine is taken up by cells via transporter proteins. Once inside a cell, cladribine undergoes phosphorylation by the enzyme deoxycytidine kinase (DCK) to produce mononucleotide 2-chlorodeoxyadenosine 5’monophosphate (2-CdAMP), which is subsequently phosphorylated to the triphosphorylated active compound 2-chlorodeoxyadenosine 5’triphosphate (2-CdATP). Activated cladribine is incorporated into cellular DNA, which triggers apoptosis. Accumulation of cladribine into cells is dependent on the ratio of DCK and 5'-nucleotidase (5’-NT), which breaks down and inactivates the compound. This ratio differs between cell types, with high levels in T and B lymphocytes, resulting in selective targeting of these cells. In contrast, DCK:5'NT is relatively low in other cell types, thus sparing numerous non-haematological cells.[11][7]
It is on the World Health Organization's List of Essential Medicines.[13]