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• W1977560862 abstract "Background: Tacrolimus metabolism depends on CYP3A4 and CYP3A5. We aimed to determine the relationship between the CYP3A4*22 polymorphism and combined CYP3A genotypes with tacrolimus disposition in pediatric heart transplant recipients. Methods: Sixty pediatric heart transplant recipients were included. Tacrolimus doses and trough concentrations were collected in the first 14 days post-transplantation. CYP3A phenotypes were defined as extensive (CYP3A5*1 + CYP3A4*1/*1 carriers), intermediate (CYP3A5*3/*3 + CYP3A4*1/*1 carriers) or poor (CYP3A5*3/*3 + CYP3A4*22 carriers) metabolizers. Results: CYP3A4*22 carriers needed 30% less tacrolimus (p = 0.016) to reach similar target concentrations compared with CYP3A4*1/*1 (n = 56) carriers. Poor CYP3A metabolizers required 17% (p = 0.023) less tacrolimus than intermediate and 48% less (p < 0.0001) than extensive metabolizers. Poor metabolizers showed 18% higher dose-adjusted concentrations than intermediate (p = 0.35) and 193% higher than extensive metabolizers (p < 0.0001). Conclusion: Analysis of CYP3A4*22, either alone or in combination with CYP3A5*3, may help towards individualization of tacrolimus therapy in pediatric heart transplant patients. Original submitted 7 January 2013; Revision submitted 10 April 2013" @default.
• W1977560862 created "2016-06-24" @default.
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• W1977560862 date "2013-07-01" @default.
• W1977560862 modified "2023-09-25" @default.
• W1977560862 title "<i>CYP3A4*22</i> and <i>CYP3A</i> combined genotypes both correlate with tacrolimus disposition in pediatric heart transplant recipients" @default.
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• W1977560862 doi "https://doi.org/10.2217/pgs.13.80" @default.
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