CYP3A4*22 and CYP3A combined genotypes both correlate with tacrolimus disposition in pediatric heart transplant recipients.

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 (CYP3A51 + CYP3A41/1 carriers), intermediate (CYP3A53/3 + CYP3A41/1 carriers) or poor (CYP3A53/3 + CYP3A422 carriers) metabolizers.

RESULTS

CYP3A422 carriers needed 30% less tacrolimus (p = 0.016) to reach similar target concentrations compared with CYP3A41/*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 CYP3A422, either alone or in combination with CYP3A53, may help towards individualization of tacrolimus therapy in pediatric heart transplant patients.