The Effects of Pharmacogenomic Variants on Calcineurin Inhibitor Metabolism

[摘要] In patients with hematologic malignancies or immunological-mediated illness, allogeneic Blood and Marrow Transplant (BMT) is utilised totransplant a new immune system. Patients undergoing BMT require early immune suppression to avoid transplant rejection and Graft vsHost illness (GVHD). Tacrolimus and cyclosporine are CNIs, while methotrexate is an antimetabolite used to suppress this immuneresponse. Tacrolimus provides data supporting oral dosage modification based on Pharmacogenomics (PGx) investigations in kidneytransplant patients for Intermediate Metabolizers (IM) and Poor Metabolizers (PM). In this arena, there are fewer researches on BMTpatients, and even fewer on the variability of IV to oral conversion dosage and the effect of first pass metabolism based on PGx profiles.Methotrexate has been demonstrated to contain PGx mutations that influence its metabolism at higher dose used for chemotherapy, althoughits effect on BMT patient dosing is unknown. According to our findings, there is statistically significant heterogeneity in Tacrolimusconcentrations based on drug test levels when compared to dosage for Intravenous (IV) and oral formulations based on PGx projectedphenotypes.

[学科分类] 药理学