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Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs characterized by a narrow therapeutic range and high pharmacokinetic variability. The effect of polymorphisms in genes related to the metabolism and transport of these drugs, namely  CYP3A4 ,  CYP3A5 ,  MDR1  and  POR  genes, has been evaluated in diverse populations. However, the impact of these polymorphisms on drug disposition is not well established in Latin American populations. Using  TaqMan ® probes, we determined the allelic frequency of seven variants in  CYP3A4 ,  CYP3A5 ,  MDR1  and  POR  in 139 Chilean renal transplant recipients, of which 89 were treated with CsA and 50 with TAC. We tested associations between variants and trough and/or 2-hour concentrations, normalized by dose (C 0 /D and C 2 /D) at specific time points post-transplant. We found that  CYP3A5*3/*3  carriers required lower doses of TAC. In TAC treated patients, most  CYP3A5*3/*3  carriers presented higher C 0 /D and a high proportion of patients with C 0  levels outside the therapeutic range relative to other genotypes. These results reinforce the value of considering  CYP3A5  genotypes alongside therapeutic drug monitoring for TAC treated Chilean kidney recipients.

Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients