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Donor CYP3A5 genotype influences tacrolimus disposition on the first day after paediatric liver transplantation
- Source :
- British Journal of Clinical Pharmacology. 83:1252-1262
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Aim The aim of the present study was to investigate the influence of the cytochrome P450 (CYP) 3A4/5 genotype in paediatric liver transplant recipients and donors, and the contribution of age and gender to tacrolimus disposition on the first day after transplantation. Methods The contribution of the CYP3A4/5 genotype in paediatric liver transplant recipients and donors to the tacrolimus blood trough concentrations (C0) and the tacrolimus concentration/weight-adjusted dose ratio on day 1 was evaluated in 67 liver-transplanted children: 33 boys and 34 girls, mean age 4.5 years. Results Donor CYP3A5 genotype appears to be significantly associated with tacrolimus disposition on the first day after liver transplantation (P < 0.0002). Other physiological factors, such as recipient age and donor gender may also play a role and lead to significant differences in tacrolimus C0 and tacrolimus concentration/weight-adjusted dose ratio on day 1. However, according to the general linear model, only recipient age appears to be independently associated with tacrolimus disposition on the first day after liver transplantation (P < 0.03). Indeed, there was a faster tacrolimus metabolism in children under 6 years of age (P < 0.02). Conclusions Donor CYP3A5 genotype, recipient age and, to a lesser extent, donor gender appear to be associated with tacrolimus disposition on day 1 after transplant. This suggests that increasing the starting tacrolimus doses in paediatric patients under 6 years of age who receive a graft from a male extensive metabolizer may enhance the possibility of their tacrolimus levels reaching the therapeutic range sooner.
- Subjects :
- 0301 basic medicine
Pharmacology
medicine.medical_specialty
CYP3A4
medicine.diagnostic_test
business.industry
medicine.medical_treatment
chemical and pharmacologic phenomena
Immunosuppression
Liver transplantation
030226 pharmacology & pharmacy
Gastroenterology
Tacrolimus
Transplantation
03 medical and health sciences
surgical procedures, operative
030104 developmental biology
0302 clinical medicine
Therapeutic drug monitoring
Internal medicine
medicine
Pharmacology (medical)
CYP3A5
business
Sex characteristics
Subjects
Details
- ISSN :
- 03065251
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- British Journal of Clinical Pharmacology
- Accession number :
- edsair.doi...........c77744d8046901ee418af654c8931c22