Effect of CYP3A5 and ABCB1 polymorphisms on the interaction between tacrolimus and itraconazole in patients with connective tissue disease

摘要: The aim of this study was to investigate the effect itraconazole (ITCZ), a potent inhibitor CYP3A4 and P-glycoprotein, on blood concentration 12 h after tacrolimus administration (C 12h) in relation CYP3A5 6986A>G ABCB1 3435C>T genotype status patients with connective tissue disease (CTD). Eighty-one CTD taking (Prograf®) once daily at night (2100 hours) were enrolled study. Whole samples collected steady state. dose-adjusted C 12h or without ITCZ co-administration significantly higher CYP3A5*3/*3 than those CYP3A5*1 allele [CYP3A5 *1/*1 vs. *1/*3 *3/*3 = 1.67 2.70 4.83 ng/mL/mg (P = 0.003) 0.68 0.97 2.20 ng/mL/mg (P < 0.001), respectively], but differences not observed for genotypes. However, there no difference increase rate between genotypes (P = 0.378 0.259). On other hand, reduction estimated glomerular filtration exhibited correlation (r = −0.482, P = 0.009). In patients, because metabolic pathway occurs only through CYP3A4, combination seems lead risk acute renal dysfunction. Therefore, we suggest that target be set as low possible dose-adjustment allele.