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• W2332638902 abstract "In Brief Background We prospectively studied renal transplant recipients receiving tacrolimus to determine the relationship between the CYP3A4, CYP3A5, and ABCB1 genetic polymorphisms and the pharmacokinetics (PK) and pharmacodynamics (PD) of tacrolimus and its metabolites. Methods Renal transplant recipients receiving tacrolimus were genotyped for CYP3A4*4, CYP3A4*5, CYP3A4*18, CYP3A5*3, ABCB1 c.1236C→T, ABCB1 c.2677G→A/T, and ABCB1 c.3435C→T. Dose-adjusted trough concentration (C0) of tacrolimus and its metabolites (M-I and M-III) and PK and PD (T-cell and monocyte subsets) were determined on transplantation days –2, 5, 30, and 90 and correlated with the corresponding genotypes. Results The dose-adjusted C0 of tacrolimus and its metabolites and AUC0–12 were significantly higher and the mean fluorescence intensity (MFI) of HLA/DR+ in monocytes was significantly lower in patients with CYP3A5*3/*3 than in patients with CYP3A5*1/*1 or CYP3A5*1/*3. However, there was no significant difference in the dose-adjusted C0 of tacrolimus and its metabolites, PK and PD among the ABCB1 genotypes. The MFI of HLA/DR+ in monocytes showed a significant negative correlation with dose-adjusted C0 of tacrolimus and its metabolites and AUC0–12. In a multiple regression analysis, the presence of the CYP3A5*3/*3 genotype was a significant independent variable determining the dose-adjusted C0 of tacrolimus and its metabolites, AUC0–12, and the MFI of HLA/DR+ in monocytes. Conclusions This study demonstrates that the CYP3A5 genetic polymorphisms are associated with the individual differences in PK and PD as well as in C0 of tacrolimus and its metabolites. The MFI of HLA/DR+ in monocytes might be considered to be a significant tool for monitoring tacrolimus efficacy. Supplemental digital content is available in the article." @default.
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• W2332638902 date "2013-03-27" @default.
• W2332638902 modified "2023-09-25" @default.
• W2332638902 title "CYP3A and ABCB1 Genetic Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Tacrolimus and Its Metabolites (M-I and M-III)" @default.
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• W2332638902 doi "https://doi.org/10.1097/tp.0b013e31827eef57" @default.
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