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. 2021 Jan 11;11(1):443.
doi: 10.1038/s41598-020-79574-7.

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

Michele Pinon  1 , Amedeo De Nicolò  2 , Antonio Pizzol  3 , Miriam Antonucci  2 , Antonio D'Avolio  2 , Loredana Serpe  4 , Dominic Dell'Olio  5 , Silvia Catalano  6 , Francesco Tandoi  6 , Renato Romagnoli  6 , Roberto Canaparo  4 , Pier Luigi Calvo  3
Affiliations

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

Michele Pinon et al. Sci Rep. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Daily TAC blood concentration after liver transplant. TAC, tacrolimus.
Figure 2
Figure 2
TAC blood concentrations on the 10th post-transplant day stratified by GRWR and the donor CYP3A5 genotype. TAC, tacrolimus; GRWR, Graft-to-Recipient Weight Ratio.
Figure 3
Figure 3
Proposal for an algorithm for a genotype and GRWR guided TAC starting dose. TAC, tacrolimus; GRWR, Graft-to-Recipient Weight Ratio.
See this image and copyright information in PMC

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