Pharmacodynamics Unlike the similarly named tacrolimus,<unk>  is not a calcineurin inhibitor, but it has a similar suppressive effect on the immune system.<unk>  inhibits IL-2 and other cytokine receptor-dependent signal transduction mechanisms, via action on mTOR, and thereby blocks activation of T and B cells. Ciclosporin and tacrolimus inhibit the secretion of IL-2, by inhibiting calcineurin. The mode of action of<unk>  is to bind the cytosolic protein FK-binding protein 12 (FKBP12) in a manner similar to tacrolimus. Unlike the tacrolimus-FKBP12 complex, which inhibits calcineurin (PP2B), the<unk> -FKBP12 complex inhibits the mTOR (mammalian Target Of Rapamycin, rapamycin being another name for<unk>  pathway by directly binding to mTOR Complex 1 (mTORC1). mTOR has also been called FRAP (FKBP-rapamycin-associated protein), RAFT (rapamycin and FKBP target), RAPT1, or SEP. The earlier names FRAP and RAFT were coined to reflect the fact that<unk>  must bind FKBP12 first, and only the FKBP12-sirolimus complex can bind mTOR. However, mTOR is now the widely accepted name, since Tor was first discovered via genetic and molecular studies of<unk> -resistant mutants of Saccharomyces cerevisiae that identified FKBP12, Tor1, and Tor2 as the targets of<unk>  and provided robust support that the FKBP12-sirolimus complex binds to and inhibits Tor1 and Tor2. Pharmacokinetics<unk>  is metabolized by the CYP3A4 enzyme and is a substrate of the P-glycoprotein (P-gp) efflux pump. It has an elimination half-life of 57–63 hours. The absorption of<unk>  into the blood stream from the intestine varies widely between patients, with some patients having up to eight times more exposure than others for the same dose. Drug levels are, therefore, taken to make sure patients get the right dose for their condition. This is determined by taking a blood sample before the next dose, which gives the trough level. However, good correlation is noted between trough concentration levels and drug exposure, known as area under the concentration-time curve, for both<unk>  <unk>  and tacrolimus (TAC) <unk> : r2 = 0.83; TAC: r2 = 0.82), so only one level need be taken to know its pharmacokinetic (PK) profile. PK profiles of<unk>  and of TAC are unaltered by simultaneous administration. Dose-corrected drug exposure of TAC correlates with<unk>  (r2 = 0.8), so patients have similar bioavailability of both.
Sirolimus
Tacrolimus
Temsirolimus
Pimecrolimus
Rituximab
Tofacitinib
Adalimumab
Lenalidomide