MDR-1 AND CYP P450 GENE POLYMORPHISMS AND 12-HR AUC PHARMACOKINETICS OF TACROLIMUS.

P725 Aims: There is a great inter- and intrapatient variability in the oral farmacokinetics of tacrolimus (Tac). Both polymorphisms of the P-glycoprotein system (MDR-1), regulating the uptake of Tac, and of the Cytochrome p450 enzyme system (CYP3A4, CYP3A5), regulating the elimination of Tac, may be of importance. Data on trough-level (C0) have been shown that CYP3A4polymorphism, but not MDR-1polymorfism, influences the dose normalised trough-level (C0). However, no information exists on the relationship of polymorphisms in these systems and the ora; biovailabiltiy (AUC), Cmax and Tmax. Methods: In 38 renal transplant recipients with a stable Tac trough-level a 12-hour time-concentration profile of Tac was performed. The influence of polymorphisms of MDR-1 (CC/CT/TT), CYP3A4 (AA/AG/GG) and CYP3A5 (AA/AG/GG) on the dose-normalised (dn) AUC (ng*h/mL per mg/kg), Cmax (ng/mL), Tmax (h), and C0 (ng/mL per mg/kg) was analysed by non-parametric statistics (Kruskal-Wallis). Results: Median values; *P ≤ 0,01 Conclusions: Polymorphisms of the CYP genes are related to differences in AUC but not in Cmax or Tmax. MDR-1 polymorphism has no significant relationship with the tested parameters.Figure