CYP3A5 and CYP3A4 , but not ABCB1 Polymorphisms Affect Tacrolimus Dose-Adjusted Trough Concentrations in Kidney Transplant Recipients

Abstract

Our results confirm the impact of the CYP3A4*22 allele on TAC pharmacokinetics, as a second significant genetic factor (in addition to the CYP3A5*1 allele) influencing TAC dose-adjusted blood concentrations in kidney transplant recipients.

Impact of PPARA and POR polymorphisms on tacrolimus pharmacokinetics and new-onset diabetes in kidney transplant recipients

“…The CYP3A5 genotype showed a significant influence on TAC pharmacokinetics, as was evidenced in the study involving the same patients: CYP3A5 expressers were characterized by significantly higher weight-adjusted TAC doses along with markedly lower C 0 and doseadjusted C 0 values starting from 1 month after transplantation [12]. For this reason, the influence of PPARA and POR genotypes on TAC pharmacokinetics was analyzed in entire study group and in subgroups stratified by CYP3A5 status.…”

“…The characteristics of the study patients are presented in Supplementary Table 1 (Supplemental digital content 1, http://links.lww.com/FPC/A738). The treatment protocol consisted of TAC, mycophenolate mofetil, and steroids, described elsewhere [12]. TAC whole blood trough concentration (C 0 ) was assessed using a chemiluminescent microparticle immunoassay (Architect Tacrolimus Assay, Abbott, Germany).…”

The Monitoring of Immunosuppressive Therapy with Tacrolimus in Patients with Kidney Transplant, Based on the Pharmacokinetic Criteria

“…Corticotherapy may also represent a significant underlying factor, since it uses the same isoenzymes of cytochrome P 450 for byotransformation (CYP3A4), leading to a decrease of tacrolimus level in the blood, having a slight enzymatic inductor effect [15]. Another important element is the age of renal allograft, the patients age at the moment of transplant, the medication administered for other comorbidities such as calcium-channel blockers (felodipine) for the treatment of hypertension -4 patients from group 1 and 2 patients from group 2 [16]; theophylline for the treatment of asthma -1 patient from group 1 [17], ketoconazole, inhibitor of CYP3A4, for the treatment of mycotic infections -2 patients from group 1 and 1 patient from group 2 [18],the patients' diet (grapefruit juice, intake of pomelo, foods that may act as enzymatic inhibitors of CYP3A4) [19,20], CYP3A4 polymorphism [21]. All of the above …”

Investigation of CYP 3A5 and ABCB1 gene polymorphisms in the long-term following renal transplantation: Effects on tacrolimus exposure and kidney function

“…Genetic variability in the ABCB1 gene results in inter-individual differences in its expression and activity. The most studied ABCB1 gene polymorphism is 3435C>T, but its role in Tac pharmacokinetics remains controversial (9,10). Considering CYP 3A5 and ABCB1 polymorphisms, the majority of pharmacogenetic studies have investigated their influence on Tac pharmacokinetics and pharmacodynamics in the early period following renal transplantation up to 1 year post-transplant, while data from subsequent periods are insufficient (5,11).…”