preview

Sirolimus Research Paper

Decent Essays

Siroimus is a potent immunosuppressive drug widely used in organ transplantation. It is a macrocyclic triene antibiotic produced by Streptomyces hygroscopicus. Siroimus was first isolated as antifungal drug. However, further studies showed its remarkable antitumor and immunosuppressive activities. Sirolimus has a potent inhibitory effect on antigen-induced proliferation of T and B lymphocytes, and inhibits antibody production. Sirolimus binds to the intracellular protein, FKBP12. The sirolimus:FKPB12 complex interacts with and blocks the activation of an essential cell-cycle kinase named mTOR (mammalian target of rapamycin). By interfering with the mTOR function, sirolimus prevents the mTOR-mediated signal-transduction pathways and consequently, this results in the blockage of cell-cycle progression in G1 …show more content…

Siroimus -induced pneumonitis has also been reported. In contrast to CNIs, sirolimus is not associated with nephrotoxicity. Therefore, it can be used as an alternative immunosuppressive agent for transplant recipients who develop renal impairment with ciclosporin or tacrolimus therapy (Knechtle, 2014). Sirolimus is rapidly absorbed from the gastrointestinal tract following oral administration and reaches its peak concentration in 1-2 hours. After absorption, sirolimus is extensively bound to red blood cells and less than 5% of the drug remains free in the plasma. Sirolimus has a relatively low bioavailability (around 25%). It is metabolized in the liver and the intestinal wall by the CYP3A enzyme subfamily (CYP3A4 and CYP3A5) and to a minor extent by CYP2C8. Sirolimus has a long elimination half-life about 60 hours in renal transplant recipients. It has a narrow therapeutic index and theraputic drug monitoring of blood levels is essential to ensure safe and effective treatment (Knechtle,

Get Access