Romanian Society of Pharmaceutical Sciences
 

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INSIGHT INTO THE POTENTIAL INFLUENCE OF INTER- AND INTRA-INDIVIDUAL VARIABILITY OF TACROLIMUS EXPOSURE ON GRAFT FUNCTION DECLINE IN THREE-YEAR PERIOD FOLLOWING KIDNEY TRANSPLANTATION

NIKOLA Z. STEFANOVIĆ 1*, RADMILA M. VELIČKOVIĆ-RADOVANOVIĆ 2,3, KATARINA S. DANKOVIĆ 4, ALEKSANDRA K. CATIĆ-DJORDJEVIĆ 1, IVANA D. DAMNJANOVIĆ 1, BRANKA P. MITIĆ 3,5, MINA B. CVETKOVIĆ 3,4, TATJANA P. CVETKOVIĆ 3,6

1.University of Nis, Faculty of Medicine, Department of Pharmacy, 81 Dr Zorana Djindjica Boulevard, 18000, Nis, Serbia
2.University of Nis, Faculty of Medicine, Department of Pharmacology with Toxicology, 81 Dr Zorana Djindjica Boulevard, 18000, Nis, Serbia
3.Clinical Centre Nis, Clinic of Nephrology, 48 Dr Zorana Djindjica Boulevard, 18000, Nis, Serbia
4.University of Nis, Faculty of Medicine, 81 Dr Zorana Djindjica Boulevard, 18000, Nis, Serbia
5.University of Nis, Faculty of Medicine, Department of Internal Medicine, 81 Dr Zorana Djindjica Boulevard, 18000, Nis, Serbia
6.University of Nis, Faculty of Medicine, Department of Biochemistry, 81 Dr Zorana Djindjica Boulevard, 18000, Nis, Serbia

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The main goal of the present study was to evaluate the association of tacrolimus (Tac) exposure parameters (trough concentration (TTC), dose-adjusted TTC (C0/D)), Tac intra-individual variability (IPV), and Tac-related gene polymorphisms (CYP3A5 and ABCB1) with kidney function in three-year period after kidney transplantation (Tx). The study enrolled 103 Caucasian patients who were genotyped on CYP3A5 6986A>G and ABCB1 3435C>T polymorphism. High IPV, lower average C0/D, kidney function at 6 months post-transplantation, and acute rejection were independent predictors of worse eGFR values between 13 and 36 months after Tx. Significant eGFR decline was observed in the low C0/D (p = 0.010) and high IPV patients’ group (p = 0.018) between 13 - 24 and 25 - 36 months. The carriers of CYP3A5*1 allele had lower C0/D values compared to the CYP3A5*3/*3 carriers during entire observation period, while ABCB1 3435 gene polymorphism did not affect C0/D. Tailoring Tac treatment based on IPV, C0/D and CYP3A5 genotype in clinical practice may identify patients at risk for graft function decline.