Impact of CYP3A5 and ABCBL polymorphisms on drug switching from cyclosporine to tacrolimus for individualized treatment of renal transplant recipients / 第二军医大学学报

ABSTRACT

Objective To investigate the impact of CYP3A5 and ABCB1 polymorphisms on the initial individualized treatment with tacrolimus (FK506) in renal transplant recipients during switching from cyclosporine (CsA) to FK506. Methods Polymerase chain reaction and restriction fragment length polymorphism method (PCR-RFLP) was employed to investigate CYP3A5 (A6989G) and ABCB1 (exon12 [C1236T], exon21G[A] 2677T and exon26 [C3435T]) genotype data. The initial trough concentration/ dose (Co/D) values were compared among different CYP3A5 genotypes in renal transplant recipients switching from CsA to FK506 using one-way ANOVA. In addition, the initial C0 /D values were also compared among different ABCB1 (exon12[C1236T], exon21G[A]2677T and exon26[C3435T]) genotypes and their haplotypes using one-way ANOVA. Results The FK506 C0 /D values were significantly different between different CYP3A5 genotypes (AA, AG and GG) at the 7th, 14th, 21th and 28th day of conversion from CsA to FK506 in renal transplant recipients CPFK506 Din CYP3A5AA group was 3. 5-fold that of CYP3A5GG group([O. 14±0. 03] mg•kg-1•d-1vs [0. 04±0. 01] mg•kg-1•d-1, P= 0. 00) and the FK506 D in CYP3A5AG group was 1. 75-fold that of CYP3A5GG group ([0. 07±0. 03] mg•kg-1•d-1vs [0. 04±0. 01] mg•kg-1•d-1, P=O. 00), the FK506 C0 in different CYP3A5 genotypes reached the same target concentration. The initial FK506 Co /D was not associated with different ABCB1 (exon12 [C1236T], exon21 G[A] 2677T and exon26 [C3435T]) genotypes or their haplotypes in renal transplant recipients. Conclusion Appropriate initial daily dose of FK506 should be selected according to CYP3A5 genotype in order to quickly achieve the target immunosuppression in renal transplant recipients who are switching immunosuppressive regimen from CsA to FK506.