The impact of CYP3A5 on the metabolism of cyclosporine A and tacrolimus in the evaluation of efficiency and safety of immunosuppressive treatment in patients after kidney transplantation

Pharmazie. 2016 Oct 1;71(10):562-565. doi: 10.1691/ph.2016.6717.

Abstract

The aim of the study was to determine the impact of CYP3A5 mutation on the serum levels of immunosuppressive drugs (tacrolimus and cyclosporine A), and on the occurrence of acute rejection episodes among patients after kidney transplantation. A limited number of such research in Polish patients was also an important factor encouraging to perform the study. Fifty-two persons were recruited. The tested patients underwent kidney transplantation and were treated either with cyclosporine A (17 persons) or with tacrolimus (35 persons). The group included 21 women and 31 men. DNA was isolated from whole blood and a modified Van Schaik et al. (2002) PCR-RFLP method was used for genotyping. The serum levels were controlled at the 7th, 14th, 30th, 90th, 180th and 360th day after transplantation. The CYP3A5 genotype had no impact on the concentrations of cyclosporine A and tacrolimus at any investigated time point. No correlation between the rate of acute rejection episodes and different genotypes of the CYP3A5 isoenzyme could be proven.

MeSH terms

  • Cyclosporine / adverse effects
  • Cyclosporine / metabolism*
  • Cyclosporine / therapeutic use*
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism*
  • DNA / genetics
  • Female
  • Genotype
  • Graft Rejection / genetics
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / metabolism*
  • Immunosuppressive Agents / therapeutic use*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Kidney Transplantation / methods*
  • Male
  • Mutation
  • Poland
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length / genetics
  • Tacrolimus / adverse effects
  • Tacrolimus / metabolism*
  • Tacrolimus / therapeutic use*

Substances

  • Immunosuppressive Agents
  • Isoenzymes
  • Cyclosporine
  • DNA
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • Tacrolimus