Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Traditional IUPAC Name
pKa (strongest acidic)
pKa (Strongest Basic)
Dược Lực Học :
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.
Cơ Chế Tác Dụng :
An antineoplastic agent used in the treatment of lymphoproliferative diseases including hairy-cell leukemia. [PubChem]
Cladribine is structurally related to fludarabine and pentostatin but has a different mechanism of action. Although the exact mechanism of action has not been fully determined, evidence shows that cladribine is phosphorylated by deoxycytidine kinase to the nucleotidecladribine triphosphate (CdATP; 2-chloro-2′-deoxyadenosine 5′-triphosphate), which accumulates and is incorporated into DNA in cells such as lymphocytes that contain high levels of deoxycytidine kinase and low levels of deoxynucleotidase, resulting in DNA strand breakage and inhibition of DNA synthesis and repair. High levels of CdATP also appear to inhibit ribonucleotide reductase, which leads to an imbalance in triphosphorylated deoxynucleotide (dNTP) pools and subsequent DNA strand breaks, inhibition of DNA synthesis and repair, nicotinamide adenine dinucleotide (NAD) and ATP depletion, and cell death. Unlike other antimetabolite drugs, cladribine has cytotoxic effects on resting as well as proliferating lymphocytes. However, it does cause cells to accumulate at the G1/S phase junction, suggesting that cytotoxicity is associated with events critical to cell entry into S phase. It also binds purine nucleoside phosphorylase (PNP), however no relationship between this binding and a mechanism of action has been established.
Dược Động Học :
▧ Absorption :
Oral bioavailability is 34 to 48%.
▧ Volume of Distribution :
* 4.5 ± 2.8 L/kg [patients with hematologic malignancies]
* 9 L/kg
▧ Protein binding :
▧ Metabolism :
Metabolized in all cells with deoxycytidine kinase activity to 2-chloro-2'-deoxyadenosine-5'-triphosphate
▧ Half Life :
▧ Clearance :
* 978 +/- 422 mL/h/kg
Độc Tính :
Symptoms of overdose include irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia and thrombocytopenia.
Chỉ Định :
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.
Tương Tác Thuốc :
Immunosuppressants such as cladribine may enhance the adverse/toxic effect of leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Consider eliminating the use of a leflunomide loading dose in patients who are receiving other immunosuppressants in order to reduce the risk for serious adverse events such as hematologic toxicity. Also, patients receiving both leflunomide and another immunosuppressive medication should be monitored for bone marrow suppression at least monthly throughout the duration of concurrent therapy.
Immunosuppressants such as cladribine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as cladribine. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
Roflumilast may enhance the immunosuppressive effect of immunosuppressants such as cladribine. The Canadian roflumilast product monograph recommends avoiding concurrent use of roflumilast with any immunosuppressant medications due to the antiinflammatory/immune altering effects of roflumilast and the lack of relevant clinical experience with such use. Of note, this recommendation to avoid concurrent use does not apply to either inhaled corticosteroids (which have much more limited systemic immune-suppressing actions) or short-term systemic corticosteroid use. U.S. prescribing information does not contain this warning; but it appears prudent to avoid this combination when possible.
Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants such as tacrolimus. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Liều Lượng & Cách Dùng :
Solution - Intravenous
Dữ Kiện Thương Mại
Nhà Sản Xuất
Sản phẩm biệt dược : Leustatin
Sản phẩm biệt dược : Litak
Sản phẩm biệt dược : Movectro
Sản phẩm biệt dược : Mylinax
Tài Liệu Tham Khảo Thêm
National Drug Code Directory