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CYP3A4*22 and CYP3A combined genotypes both correlate with tacrolimus disposition in pediatric heart transplant recipients.
- Source :
-
Pharmacogenomics [Pharmacogenomics] 2013 Jul; Vol. 14 (9), pp. 1027-36. - Publication Year :
- 2013
-
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.<br />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.<br />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).<br />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.
- Subjects :
- Alleles
Child
Child, Preschool
Dose-Response Relationship, Drug
Female
Gene Expression genetics
Humans
Immunosuppressive Agents administration & dosage
Male
Polymorphism, Genetic
Retrospective Studies
Tissue Donors
Cytochrome P-450 CYP3A genetics
Genotype
Heart Transplantation
Tacrolimus administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1744-8042
- Volume :
- 14
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Pharmacogenomics
- Publication Type :
- Academic Journal
- Accession number :
- 23837477
- Full Text :
- https://doi.org/10.2217/pgs.13.80