Early impact of donor CYP3A5 genotype and Graft-to-Recipient Weight Ratio on tacrolimus pharmacokinetics in pediatric liver transplant patients
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 me...
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| Published in | Scientific reports Vol. 11; no. 1; pp. 443 - 13 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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London
Nature Publishing Group UK
11.01.2021
Nature Publishing Group Nature Portfolio |
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| ISSN | 2045-2322 2045-2322 |
| DOI | 10.1038/s41598-020-79574-7 |
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| 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. |
|---|---|
| AbstractList | 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. 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. 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.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. 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. 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. |
| ArticleNumber | 443 |
| Author | D’Avolio, Antonio Pizzol, Antonio Antonucci, Miriam Calvo, Pier Luigi Tandoi, Francesco Romagnoli, Renato Pinon, Michele Canaparo, Roberto Catalano, Silvia De Nicolò, Amedeo Serpe, Loredana Dell’Olio, Dominic |
| Author_xml | – sequence: 1 givenname: Michele surname: Pinon fullname: Pinon, Michele email: michele.pinon@gmail.com organization: Pediatric Gastroenterology Unit, Regina Margherita Children’s Hospital, AOU Città della Salute e della Scienza di Torino, University of Turin – sequence: 2 givenname: Amedeo surname: De Nicolò fullname: De Nicolò, Amedeo organization: Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital – sequence: 3 givenname: Antonio surname: Pizzol fullname: Pizzol, Antonio organization: Pediatric Gastroenterology Unit, Regina Margherita Children’s Hospital, AOU Città della Salute e della Scienza di Torino, University of Turin – sequence: 4 givenname: Miriam surname: Antonucci fullname: Antonucci, Miriam organization: Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital – sequence: 5 givenname: Antonio surname: D’Avolio fullname: D’Avolio, Antonio organization: Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital – sequence: 6 givenname: Loredana surname: Serpe fullname: Serpe, Loredana organization: Department of Drug Science and Technology, University of Turin – sequence: 7 givenname: Dominic surname: Dell’Olio fullname: Dell’Olio, Dominic organization: Regional Transplant Center, AOU Città della Salute e della Scienza di Torino – sequence: 8 givenname: Silvia surname: Catalano fullname: Catalano, Silvia organization: General Surgery, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin – sequence: 9 givenname: Francesco surname: Tandoi fullname: Tandoi, Francesco organization: General Surgery, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin – sequence: 10 givenname: Renato surname: Romagnoli fullname: Romagnoli, Renato organization: General Surgery, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin – sequence: 11 givenname: Roberto surname: Canaparo fullname: Canaparo, Roberto organization: Department of Drug Science and Technology, University of Turin – sequence: 12 givenname: Pier Luigi surname: Calvo fullname: Calvo, Pier Luigi organization: Pediatric Gastroenterology Unit, Regina Margherita Children’s Hospital, AOU Città della Salute e della Scienza di Torino, University of Turin |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33432012$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_j_jpba_2021_114315 crossref_primary_10_3390_pharmaceutics14122739 crossref_primary_10_1111_petr_70032 crossref_primary_10_1111_petr_14044 crossref_primary_10_1155_2022_7647754 |
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| Snippet | Tacrolimus (TAC) pharmacokinetics is influenced by the donor
CYP3A5
genotype and the age of pediatric liver recipients. However, an optimization of a... Tacrolimus (TAC) pharmacokinetics is influenced by the donor CYP3A5 genotype and the age of pediatric liver recipients. However, an optimization of a... Abstract Tacrolimus (TAC) pharmacokinetics is influenced by the donor CYP3A5 genotype and the age of pediatric liver recipients. However, an optimization of a... |
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| Title | Early impact of donor CYP3A5 genotype and Graft-to-Recipient Weight Ratio on tacrolimus pharmacokinetics in pediatric liver transplant patients |
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