Abstract
Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients). The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc). The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC). In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%). Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation.
Highlights
Lung transplantation is the option for a variety of end-stage pulmonary diseases
The pharmacokinetics of Tac and mycophenolic acid (MPA) are characterized by important inter-patient variability and poor bioavailability
This situation is severe in lung transplantation patients, where high variability in drug concentrations has been reported [16]
Summary
Lung transplantation is the option for a variety of end-stage pulmonary diseases. It remains as the solid organ transplant with the poorest outcomes, with less than 80% and 70% survival after one and three years, respectively [1]. Solid organ transplant therapy includes treatment with broad-spectrum immunosuppressive regimens, usually calcineurin antagonists (cyclosporin (Cs) and tacrolimus (Tac)) together with mycophenolic acid (MPA). These drugs have a narrow therapeutic index and important inter-individual variability in their pharmacokinetic profile. Identifying the contributing factors that account for variation in blood drug concentrations is of major importance in these patients and can be used to optimize therapeutic strategies and increase the benefit—Risk ratio of immunosuppressive therapy
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