Cytochrome P450 genetic polymorphisms influence the serum concentration of calcineurin inhibitors in allogeneic hematopoietic SCT recipients

Effect of Genetic Polymorphism of CYP3A5 and CYP2C19 and Concomitant Use of Voriconazole on Blood Tacrolimus Concentration in Patients Receiving Hematopoietic Stem Cell Transplantation

“…However, a large interindividual variability in blood TAC concentration has been reported in patients who had received HSCT even though TAC was administered intravenously. 6,18 The most frequent cause of the variability of blood TAC concentration has been considered to be attributable to enzyme activity against TAC metabolism because of the genetic polymorphism of CYP3A5 and drug-drug interactions. Although the magnitude of the CYP3A-mediated drug-drug interaction seems to be related to intrinsic CYP3A activity, in practice, it is still difficult to predict the magnitude of the interaction between TAC and triazole antifungal agents.…”

“…Onizuka et al 6 reported that the CYP3A5 genotype was associated with the blood concentration of TAC delivered via intravenous administration in HSCT recipients. They found that the required dose of TAC was significantly reduced from day 21 to day 28 after HSCT in recipients with CYP3A5*3/*3 genotype.…”

“…3 Although individual differences in drug response may vary because of age, sex, and disease, 4 the wide range of variability in TAC PK in HSCT recipients is often explained by polymorphisms in genes encoding metabolizing enzymes and drug interaction via metabolizing enzymes. [5][6][7] However, interindividual variability of blood TAC concentration during the early stages of HSCT is as of yet still difficult to predict.…”

Prophylactic and therapeutic treatment of graft-versus-host disease in Japan

“…The blood concentration of Tac was not necessarily high in patients who developed Tac-related encephalopathy [41]. Genetic polymorphisms of cytochrome P450 may affect the serum concentration of calcineurin inhibitors in transplant patients [42].…”

Cyclosporine and methotrexate-related pharmacogenomic predictors of acute graft-versus-host disease

“…[26][27][28] So far, only a few studies have addressed such an important phenotype-genotype relationship, although genetic variations in the gene coding for methylenetrahydrofolate reductase (MTHFR) enzyme have received great attention. 18,[22][23][24][29][30][31][32][33] As the inter-individual variability in GvHD occurrence among HSCT patients may be, at least partly, related to the genetic diversity of genes involved in the bioavailability and in the metabolism of methotrexate/cyclosporine A, we tested in this study whether selected single nucleotide polymorphisms (SNP) located in loci encoding molecules implicated in the methotrexate/cyclosporine A metabolic and transport pathways could influence the incidence of GvHD in HSCT recipients.…”