|famuyiyaom||Дата: Пятница, 13.02.2015, 11:58 | Сообщение # 1|
|Tacrolimus (also FK-506 or fujimycin, selling names Prograf, Advagraf, Protopic) is an immunosuppressive opiate that is mainly in use accustomed to after allogeneic medium transplant to trim down the activity of the passive's vaccinated method and so lower the risk of tool rejection. It is also used in a up to date preparation in the treatment of atopic dermatitis (eczema), strict refractory uveitis after bone marrow transplants, exacerbations of token transform complaint, and the husk form vitiligo. |
It is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil representative that contained the bacteria Streptomyces tsukubaensis. It reduces interleukin-2 (IL-2) forming 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 class of loam bacterium,Streptomyces tsukubaensis.[2 - The name tacrolimus is derived from 'Tsukuba macrolide immunosuppressant'.[3 -
Tacrolimus was to begin approved by the Comestibles and Downer Management (FDA) in 1994 someone is concerned end in liver transplantation; this has been extended to embrace kidney, affection, reduced bowel, pancreas, lung, trachea, overlay, cornea, bone marrow, and limb transplants.
The branded type of the dull is owned sooner than Astellas Pharma, and is sold under the trade names Prograf given twice ordinary,Advagraf, a unchanging releasing formulation allowing a single time finally day after day dosing, and Protopic (Eczemus in Pakistan past Brookes Pharma), the current formulation.[4 - Advagraf is to hand in 0.5, 1, 3 and 5 mg capsules, the not bad is concentrations of 0.1% and 0.03%.
A number two 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 assortment in blood levels compared to twice-daily tacrolimus.[5 - Figures from the premier Phase 3 litigation in steady kidney shift patients showed that this once-daily formulation was non-inferior in efficacy and sanctuary compared to twice-daily tacrolimus.[6 - A second Phase 3 trial in de novo patients is ongoing.[7 -
Mechanism of encounter
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 activate calcineurin. Calcineurin then dephosphorylates the transcription element NF-AT (atomic agent of activated T-cells), which moves to the pith of the T-cell and increases the motion of genes coding in behalf of IL-2 and common cytokines. Tacrolimus prevents the dephosphorylation of NF-AT.[8 - In group specifically, Tacrolimus reduces peptidyl-prolyl isomerase occupation by binding to the immunophilin FKBP12 (FK506 binding protein) creating a new complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin and so inhibiting both T-lymphocytesignal transduction and IL-2 transcription.[9 - Although this activity is similar to ciclosporin, studies secure shown that the frequency of dangerous renunciation is reduced by tacrolimus use done with ciclosporin.[10 - Although short-term immunosuppression anent submissive and graft survival is develop to be be like between the two drugs, tacrolimus results in a more favorable lipid portrait, and this may acquire substantial long-term implications given the prognostic act upon of also brush on insert survival.[11 -
From http://www.fmyykj.com - suzhou pharmaceutical technology co.,ltd.