Early impact of donor CYP3A5 genotype and Graft-to-Recipient Weight Ratio on tacrolimus pharmacokinetics in pediatric liver transplant patients.
Adolescent
Age Factors
Body Weight
/ physiology
Child
Child, Preschool
Cohort Studies
Cytochrome P-450 CYP3A
/ genetics
Drug Monitoring
Female
Genotype
Graft Rejection
/ epidemiology
Humans
Immunosuppressive Agents
/ pharmacokinetics
Infant
Liver
Liver Transplantation
Male
Organ Size
Postoperative Period
Tacrolimus
/ administration & dosage
Tissue Donors
Transplants
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 01 2021
11 01 2021
Historique:
received:
22
03
2020
accepted:
20
10
2020
entrez:
12
1
2021
pubmed:
13
1
2021
medline:
27
8
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33432012
doi: 10.1038/s41598-020-79574-7
pii: 10.1038/s41598-020-79574-7
pmc: PMC7801660
doi:
Substances chimiques
Immunosuppressive Agents
0
CYP3A5 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP3A
EC 1.14.14.1
Tacrolimus
WM0HAQ4WNM
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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