New immunosuppressive agents in pediatric transplantation

Abstract

Immunosuppressive therapy in pediatrics continues to evolve. Over the past decade, newer immunosuppressive agents have been introduced into adult and pediatric transplant patients with the goal of improving patient and allograft survival. Unfortunately, large-scale randomized clinical trials are not commonly performed in children. The purpose of this review is to discuss the newer immunosuppressive agents available for induction therapy, maintenance immunosuppression, and the treatment of rejection.

m-TOR Inhibitors in the Current Practice

“…Similarly, co-administration of diltiazem, verapamil, fluconazole, ketoconazole, anticonvulsants and rifampicin can altered the AUC of sirolimus [5,7,23].…”

“…Beyond that, the efficacy of both drugs appears to be similar, as well as their toxicity profiles [7,[25][26][27][28].…”

“…It is metabolized by both cytochrome P450 IIIA4 (CYP3A4) and Pglycoprotein, which explains the interactions with other drugs and high-fat meals and their metabolites are eradicated through gastrointestinal tract (91%) and kidneys [7,[18][19][20][21].…”

“…In contrast to SRL, everolimus (EVR/RAD/Certican) is considered as a derivative of sirolimus, structurally looks similar to SLR but with additional extra hydroxyethyl chain substitution at position-40 on the sirolimus molecule, which make it more hydrophilic and bioavailable than sirolimus (figure 2) [1,4,5,[7][8][9][10][11][12][13][14][15]. Similarly EVR/FKBP-12 multiplexes acts directly to mTOR, leading to inhibition of T-cell progression from the G1 to the S stage of cell cycle, thus results in inhibition of IL-2-induced protein synthesis and cellular proliferation and inhibition of IL-4-dependent multiplications of T-and B-cells [1,4,15,16].…”

“…and acts through the co-stimulatory and cytokine-driven pathways, to prevent the signal III pathway (G1 to S transition, interpretation, and cytokine-driven T-cell multiplication) [1,[4][5][6][7][8][9][10]. The serine/threonine kinase mTOR is a downstream effector of the PI3K/AKT pathway, and forms two distinct multiprotein complexes, mTORC1 and mTORC2 (figure 1).…”