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Tacrolimus
drug data and news
Tacrolimus drug data, resources, and news articles (when available). Onconews.org provides news on cancer research. This section, which includes profiles on medicines that may or not be cancer-related is in beta form. If things run smoothly we will be releasing a new format late in the summer of 2006.
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| Generic name | Tacrolimus | ||
| Brand Names/Synonyms | FK 506; FK-506; FK5; K506; Prograf; Protopic; Tacarolimus; Tacrolimus | ||
| Indication | Tacrolimus is indicated for the prophylaxis of organ rejection in patients receiving allogeneic liver or kidney transplants. Used in a topical preparation in the treatment of severe atopic dermatitis, also used after bone marrow transplants and for severe refractory uveitis. | ||
| Sponsored links | Description | Not Available | |
| Pharmacology | Tacrolimus, a macrolide immunosuppressant produced by Streptomyces tsukubaensis, is an immunosuppressive agent indicated for the treatment of patients receiving kidney and/or liver transplants. Tacrolimus has been demonstrated to suppress humoral immunity and, to a greater extent, cell-mediated reactions such as allograft rejection, delayed type hypersensitivity, collagen- induced arthritis, experimental allergic encephalomyelitis, and graft versus host disease. It has similar immunosuppressive properties to cyclosporine, but is much more potent in equal volumes. | ||
| Mechanism Of Action | Tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12. A complex of Tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin is inhibited. This prevents the dephosphorylation and translocation of nuclear factor of activated T-cells (NF-AT), a nuclear component thought to initiate gene transcription for the formation of lymphokines. Tacrolimus also inhibits the transcription for genes which encode IL-3, IL-4, IL-5, GM-CSF, and TNF-, all of which are involved in the early stages of T-cell activation. Additionally, Tacrolimus has been shown to inhibit the release of pre-formed mediators from skin mast cells and basophils, and to downregulate the expression of FceRI on Langerhans cells. | ||
| Tacrolimus News (When available) |
Possible New Treatment For Stroke Victims 16 May 2006 Eczema on Infants' Arms and Joints Linked to Future Atopic ... May 15, 2006 International Approvals: Omnitrope, Prograf, Cetrotide May 1, 2006 Chronic Hepatitis Common in Kids After Liver Transplant May 4, 2006 Prograf Now Approved for Prophylaxis Use in Heart Transplantation ... Apr 21, 2006 NICE Issues Guidance On Immunosuppressive Therapy For Young Kidney ... Apr 27, 2006 Astellas Pharma's Immunosuppressant Prograf Now Available in ... Apr 24, 2006 | ||
| Dosage Forms | CAPSULE; OINTMENT; SOLUTION | ||
| Drug_Category | Immunosuppressive Agents; ATC:D11AX14; ATC:L04AA05 | ||
| Absorption | Generally incomplete with absolute bioavailability of 17-22% | ||
| Interactions |
-->Interactions for Tacrolimus: Formal topical drug interaction studies with PROTOPIC Ointment have not been conducted. Based on its minimal extent of absorption, interactions of PROTOPIC Ointment with systemically administered drugs are unlikely to occur but cannot be ruled out. The concomitant administration of known CYP3A4 inhibitors in patients with widespread and/or erythrodermic disease should be done with caution. Some examples of such drugs are erythromycin, itraconazole, ketoconazole, fluconazole, calcium channel blockers and cimetidine. | ||
| Toxicity | Side effects can be severe and include blurred vision, liver and kidney problems (it is nephrotoxic), seizures, tremors, hypertension, hypomagnesemia, diabetes mellitus, hyperkalemia, itching, insomnia, confusion. LD50=134-194 mg/kg (rat) | ||
| Organisms Affected | Humans and other mammals | ||
| Chemical IUPAC Name | [3S-[3R*[E(1S*,3S*,4S*)],4S*,5R*,8S*,9E,12R*,14R*,15S*,16R*,18S*,19S*,26aR*]]-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5, 19-dihydroxy-3- [2-(4-hydroxy-3-methoxycyclohexyl) -1-methylethenyl]-14, 16-dimethoxy-4,10,12,18-tetramethyl-8-(2-propenyl)-15, 19-epoxy-3H-pyrido[2,1-c][1,4] oxaazacyclotricosine-1,7,20, 21(4H,23H)-tetrone, monohydrate | ||
| Chemical Formula | C44H69NO12 | ||
| Molecular Weight | 804.018 g/mol | ||
| Smiles String | CC1CC(C2C(CC(C(O2)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C(CC(=O)C(C=C(C1)C)CC=C)O)C)C(=CC4CCC(C(C4)OC)O)C)O)C)OC)OC | ||
| Melting Point | 126 °C | ||
| Water Solubility | Insoluble in water, Soluble in DMSO and MeOH | ||
| State | Solid | ||
| LogP/Hphobicity | 3.534 | ||
| Isoelectric Point | Not Available | ||
| Biotransformation | Hepatic, extensive, primarily by CYP3A4. The major metabolite identified in incubations with human liver microsomes is 13-demethyl tacrolimus. In in vitro studies, a 31-demethyl metabolite has been reported to have the same activity as tacrolimus. | ||
| Half Life | 11.3 hours (range from 3.5 to 40.6 hrs) | ||
| Protein Binding [%] | 75-99% | ||
| RxList Link | RXlist | ||
| Sponsored links | |||
| Drug Reference |
http://www.drugs.com/cons/Tacrolimus.html http://www.rxlist.com/cgi/generic2/tacrolimus.htm | ||
| Drug Type | Approved Drug | ||
| Accession No | APRD00276 | ||
| CAS Registry Number | 104987-11-3 | ||
| KEGG Compound ID | C01375 | ||
| PubChem ID | SID:66564 | ||
| PharmGKB ID | PA451578 | ||
| SwissProt ID | Not Available | ||
| GenBank ID | Not Available | ||
| Drug ID Number [DIN] | 2244149 |
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