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| Primary information |
|---|
| ID | 10674 |
| Therapeutic ID | Th1147 |
| Protein Name | Natalizumab |
| Sequence | NA
|
| Molecular Weight | NA |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | 61 (FAB fr |
| Half-life | 11 ± 4 days |
| Description | Humanized IgG4k monoclonal antibody produced in murine myeloma cells. Natalizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to a4-integrin. Natalizumab was voluntarily withdrawn from U.S. market because of risk of Progressive multifocal leukoencephalopathy (PML). It was returned to market July, 2006. |
| Indication/Disease | For treatment of multiple sclerosis. |
| Pharmacodynamics | In multiple sclerosis, lesions are believed to occur when activated inflammatory cells, including T-lymphocytes, cross the blood-brain barrier (BBB). Leukocyte migration across the BBB involves interaction between adhesion molecules on inflammatory cells, and their counter-receptors present on endothelial cells of the vessel wall. The clinical effect of natalizumab in multiple sclerosis may be a secondary result of its blockade of the molecular interaction of a 4b 1-integrin expressed by inflammatory cells with VCAM-1 on vascular endothelial cells, and with CS-1 and/or osteopontin expressed by parenchymal cells in the brain. α4-integrin is required for white blood cells to move into organs, therefore, natalizumab prevents these immune cells from crossing blood vessel walls to reach affected organs thereby decreasing inflamation. |
| Mechanism of Action | Binds to the α4-subunit of α4b 1 and α4b 7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4-mediated adhesion of leukocytes to their counter-receptor(s). |
| Toxicity | NA |
| Metabolism | Most likely removed by opsonization via the reticuloendothelial system when bound to leukocytes. |
| Absorption | NA |
| 5.7 ± 1.9 L [Multiple Sclerosis (MS) Patients, 5.2 ± 2.8 L [Crohn's Disease (CD) Patients] |
| Clearance | * 16 +/- 5 mL/hour [patients with MS who did not have PML receiving the repeat IV administration of a 300 mg dose] * 22 +/- 22 mL/hour [Patients with Crohn's Disease receiving the repeat IV administration of a 300 mg dose] |
| Categories | Amino Acids, Peptides, and Proteins,Antibodies,Antibodies, Monoclonal,Antibodies, Monoclonal, Humanized,Antineoplastic and Immunomodulating Agents,Blood Proteins,Globulins,Immunoglobulins,Immunologic Factors,Immunomodulatory Agents,Immunoproteins,Immunosuppressive Agents,Integrin Receptor Antagonist,Proteins,Selective Immunosuppressants,Serum Globulins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Integrin alpha-4,Low affinity immunoglobulin gamma Fc region receptor III-B,Intercellular adhesion molecule 1,High affinity immunoglobulin gamma Fc receptor I |
| Brand Name | NA |
| Company | Biogen Idec Canada Inc |
| Brand Description | Biogen Idec Canada Inc |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | Solution |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |