Pier Luigi Calvo1, Loredana Serpe2, Andrea Brunati3, Antonello Nonnato4, Daniela Bongioanni5, Dominic Dell' Olio5, Michele Pinon1, Carlo Ferretti2, Francesco Tandoi3, Giulia Carbonaro3, Mauro Salizzoni3, Antonio Amoroso5, Renato Romagnoli3, Roberto Canaparo2. 1. Department of Pediatrics and Public Health Sciences, Division of Pediatric Gastroenterology, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy. 2. Department of Drug Science and Technology, University of Torino, Torino, Italy. 3. Department of Surgical Sciences, Liver Transplantation Center, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy. 4. Clinical Biochemistry Unit, A.O.U. Città della Salute e della Scienza of Torino, Torino, Italy. 5. Department of Medical Sciences, Regional Transplantation Center, A.O.U. Città della Salute e della Scienza of Torino, University of Torino, Torino, Italy.
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.
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:DonorCYP3A5 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:DonorCYP3A5 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.
Authors: Luis Sendra; Gladys G Olivera; Rafael López-Andújar; Cristina Serrano; Luis E Rojas; Eva María Montalvá; María José Herrero; Salvador F Aliño Journal: Pharmaceutics Date: 2022-02-03 Impact factor: 6.321
Authors: Tessa A M Mulder; Ruben A G van Eerden; Mirjam de With; Laure Elens; Dennis A Hesselink; Maja Matic; Sander Bins; Ron H J Mathijssen; Ron H N van Schaik Journal: Front Genet Date: 2021-07-08 Impact factor: 4.599