|fmyykjf||Дата: Суббота, 22.03.2014, 04:49 | Сообщение # 1|
|Tacrolimus (also FK-506 or fujimycin, swop names Prograf, Advagraf, Protopic) is an immunosuppressive pharmaceutical that is on the whole used after allogeneic unit displace to compress the vocation of the passive's immune approach and so debase the danger of tool rejection. It is also used in a local preparation in the treatment of atopic dermatitis (eczema), strict refractory uveitis after bone marrow transplants, exacerbations of token transform blight, and the husk form vitiligo. |
It is a 23-membered macrolide lactone discovered in 1984 from the fermentation consomm?of a Japanese filth sample that contained the bacteria Streptomyces tsukubaensis. It reduces interleukin-2 (IL-2) putting out by T-cells.
Tacrolimus was discovered in 1984; it was among the maiden macrolide immunosuppressants discovered, preceded past the development of rapamycin (sirolimus) on Rapa Nui (Easter Island) in 1975.[1 - It is produced during a breed of loam bacterium,Streptomyces tsukubaensis.[2 - The high regard tacrolimus is derived from 'Tsukuba macrolide immunosuppressant'.[3 -
Tacrolimus was beforehand approved by the Food and Cure-all Administration (FDA) in 1994 in compensation make use of in liver transplantation; this has been extended to comprehend kidney, heart, uncomfortable bowel, pancreas, lung, trachea, pellicle, cornea, bone marrow, and limb transplants.
The branded variation of the medicate is owned next to Astellas Pharma, and is sold below the career names Prograf assumption twice ordinary,Advagraf, a sustained releasing formulation allowing once constantly dosing, and Protopic (Eczemus in Pakistan on Brookes Pharma), the up to date formulation.[4 - Advagraf is handy in 0.5, 1, 3 and 5 mg capsules, the correct is concentrations of 0.1% and 0.03%.
A other once-daily formulation of tacrolimus is in Stage 3 clinical trials in the U.S. and Europe. This formulation also has a smoother pharmacokinetic vigorish that reduces the peak-to-trough rank in blood levels compared to twice-daily tacrolimus.[5 - Data from the premier Time 3 woe in reasonable kidney transplant patients showed that this once-daily formulation was non-inferior in efficacy and sanctuary compared to twice-daily tacrolimus.[6 - A aid Condition 3 effort in de novo patients is ongoing.[7 -
Logical positivism of action
Tacrolimus is chemically known as a macrolide. In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to get started calcineurin. Calcineurin then dephosphorylates the transcription factor NF-AT (nuclear agent of activated T-cells), which moves to the focus of the T-cell and increases the motion of genes coding to save IL-2 and related cytokines. Tacrolimus prevents the dephosphorylation of NF-AT.[8 - In group specifically, Tacrolimus reduces peptidyl-prolyl isomerase occupation during binding to the immunophilin FKBP12 (FK506 binding protein) creating a new complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin therefore inhibiting both T-lymphocytesignal transduction and IL-2 transcription.[9 - Although this liveliness is correspond to to ciclosporin, studies have shown that the occurrence of keen renunciation is reduced about tacrolimus exigency execrate above ciclosporin.[10 - Although short-term immunosuppression as regards submissive and extortion survival is found to be comparable between the two drugs, tacrolimus results in a more favorable lipid profile, and this may be undergoing urgent long-term implications given the prognostic play of rejection on graft survival.[11 -