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Early impact of donor CYP3A5 genotype and Graft-to-Recipient Weight Ratio on tacrolimus pharmacokinetics in pediatric liver transplant patients.
- Source :
-
Scientific reports [Sci Rep] 2021 Jan 11; Vol. 11 (1), pp. 443. Date of Electronic Publication: 2021 Jan 11. - Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Adolescent
Age Factors
Child
Child, Preschool
Cohort Studies
Female
Graft Rejection epidemiology
Graft Rejection etiology
Humans
Immunosuppressive Agents pharmacokinetics
Infant
Male
Postoperative Period
Tacrolimus administration & dosage
Body Weight physiology
Cytochrome P-450 CYP3A genetics
Drug Monitoring
Genotype
Graft Rejection prevention & control
Liver
Liver Transplantation
Organ Size
Tacrolimus pharmacokinetics
Tissue Donors
Transplants
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33432012
- Full Text :
- https://doi.org/10.1038/s41598-020-79574-7