Early impact of donor CYP3A5 genotype and Graft-to-Recipient Weight Ratio on tacrolimus pharmacokinetics in pediatric liver transplant patients.

Autor: Pinon M; Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy. michele.pinon@gmail.com., De Nicolò A; Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin, Italy., Pizzol A; Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy., Antonucci M; Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin, Italy., D'Avolio A; Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin, Italy., Serpe L; Department of Drug Science and Technology, University of Turin, Turin, Italy., Dell'Olio D; Regional Transplant Center, AOU Città della Salute e della Scienza di Torino, Turin, Italy., Catalano S; General Surgery, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy., Tandoi F; General Surgery, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy., Romagnoli R; General Surgery, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy., Canaparo R; Department of Drug Science and Technology, University of Turin, Turin, Italy., Calvo PL; Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Jan 11; Vol. 11 (1), pp. 443. Date of Electronic Publication: 2021 Jan 11.
DOI: 10.1038/s41598-020-79574-7
Abstrakt: Tacrolimus (TAC) pharmacokinetics is influenced by the donor CYP3A5 genotype and the age of pediatric liver recipients. However, an optimization of a genotype-based algorithm for determining TAC starting is needed to earlier achieve stable target levels. As the graft itself is responsible for its metabolism, the Graft-to-Recipient Weight Ratio (GRWR) might play a role in TAC dose requirements. A single-center study was carried out in a cohort of 49 pediatric recipients to analyse the impact of patient and graft characteristics on TAC pharmacokinetics during the first 15 post-transplant days. Children < 2 years received grafts with a significantly higher GRWR (4.2%) than children between 2-8 (2.6%) and over 8 (2.7%). TAC concentration/weight-adjusted dose ratio was significantly lower in recipients from CYP3A5*1/*3 donors or with extra-large (GRWR > 5%) or large (GRWR 3-5%) grafts. The donor CYP3A5 genotype and GRWR were the only significant predictors of the TAC weight adjusted doses. Patients with a GRWR > 4% had a higher risk of acute rejection, observed in 20/49 (41%) patients. In conclusion, TAC starting dose could be guided according to the donor CYP3A5 genotype and GRWR, allowing for a quicker achievement of target concentrations and eventually reducing the risk of rejection.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje