Title : Combined effects of CYP3A5*1, POR*28, and CYP3A4*22 single nucleotide polymorphisms on early concentration-controlled tacrolimus exposure in de-novo renal recipients.

Pub. Date : 2014 Dec

PMID : 25322286






3 Functional Relationships(s)
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1 RESULTS: Fast metabolizers (CYP3A5*1/POR*28T carriers) had two-fold to three-fold higher tacrolimus dose requirements compared with slow metabolizers (CYP3A5*3/*3/CYP3A4*22 carriers) and needed significantly more time to achieve the target tacrolimus C0 of a minimum 10 ng/ml (3.3+-1.7 vs. 1.34+-0.75 days; P<0.0001). Tacrolimus cytochrome p450 oxidoreductase Homo sapiens
2 Multivariate analyses identified the CYP3A5*1/POR*28/CYP3A4*22 genotype combination as the single strongest determinant of tacrolimus dose requirements throughout the first year, explaining between 24-40% of its variability, whereas recipient age, hematocrit, and delayed graft function were additional nongenetic determinants of tacrolimus dose. Tacrolimus cytochrome p450 oxidoreductase Homo sapiens
3 CONCLUSION: Combining the CYP3A5*1, POR*28 and CYP3A4*22 genotypes allows partial differentiation of early tacrolimus dose requirements and the time to reach therapeutic target concentrations after transplantation, but without obvious clinical implications. Tacrolimus cytochrome p450 oxidoreductase Homo sapiens