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• W2071760250 abstract "1. Disposition of tacrolimus and its major metabolites, 13-O-desmethyl tacrolimus and 15-O-desmethyl tacrolimus, was evaluated in stable kidney transplant recipients in relation to diabetes mellitus and genetic polymorphism of cytochrome P450 (CYP) 3A.2. Steady-state concentration–time profiles were obtained for 12-hour or 2-hour post-dose, in 20 (11 with diabetes) and 32 (24 with diabetes) patients, respectively. In addition, single nucleotide polymorphisms of the following genes: CYP3A4 (CYP3A4: CYP3A4*1B, −392A > G), 3A5 (CYP3A5: CYP3A5*3, 6986A > G) and P-glycoprotein (ABCB1: 3435C > T) were characterized.3. Dose-normalized concentrations of tacrolimus or metabolites were higher in diabetic patients. CYP3A4*1B carriers and CYP3A5 expressers, independently or when assessed as a combined CYP3A4-3A5 genotype, had significantly lower dose-normalized pre-dose (C0/dose) and 2-hour post-dose (C2/dose) concentrations of tacrolimus and metabolites. Non-diabetic patients with at least one CYP3A4*1B and CYP3A5*1 allele had lower C0/dose as compared to the rest of the population.4. Genetic polymorphism of CYP3A5 or CYP3A4 influence tacrolimus or metabolites dose-normalized concentrations but not metabolite to parent concentration ratios. The effect of diabetes on tacrolimus metabolism is subject to debate and requires a larger sample size of genetically stratified subjects." @default.
• W2071760250 created "2016-06-24" @default.
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• W2071760250 date "2013-01-02" @default.
• W2071760250 modified "2023-10-16" @default.
• W2071760250 title "Concentration of tacrolimus and major metabolites in kidney transplant recipients as a function of diabetes mellitus and cytochrome P450 3A gene polymorphism" @default.
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• W2071760250 doi "https://doi.org/10.3109/00498254.2012.752118" @default.
• W2071760250 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4116556" @default.
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