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  • Effect of CYP3A4 , CYP3A5 ,...
    Contreras-Castillo, Stephania; Plaza, Anita; Stojanova, Jana; Navarro, Gustavo; Carmona, Rodolfo; Corvalán, Fernando; Cerpa, Leslie; Sandoval, Christopher; Muñoz, Daniel; Leiva, Marina; Castañeda, Luis E; Farias, Nayaret; Alvarez, Carolina; Llull, Gabriel; Mezzano, Sergio; Ardiles, Leopoldo; Varela, Nelson; Rodríguez, María S; Flores, Claudio; Cayún, Juan Pablo; Krall, Paola; Quiñones, Luis A

    Frontiers in pharmacology, 12/2021, Letnik: 12
    Journal Article

    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 , , and 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 ® probes, we determined the allelic frequency of seven variants in , , and 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 /D and C /D) at specific time points post-transplant. We found that carriers required lower doses of TAC. In TAC treated patients, most carriers presented higher C /D and a high proportion of patients with C levels outside the therapeutic range relative to other genotypes. These results reinforce the value of considering genotypes alongside therapeutic drug monitoring for TAC treated Chilean kidney recipients.