Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation
The evidence available in the pediatric population is limited for making clinical decisions regarding the optimization of tacrolimus (TAC) in pharmacotherapy. The objective of this study was to estimate the frequency of CYP3A5 genetic polymorphisms and their relationship with tacrolimus requirements...
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MDPI AG
2020-09-01
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| 丛编: | Pharmaceutics |
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| 在线阅读: | https://www.mdpi.com/1999-4923/12/9/898 |
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| author | Jefferson Antonio Buendía Esteban Halac Andrea Bosaleh María T. Garcia de Davila Oscar Imvertasa Guillermo Bramuglia |
| author_facet | Jefferson Antonio Buendía Esteban Halac Andrea Bosaleh María T. Garcia de Davila Oscar Imvertasa Guillermo Bramuglia |
| author_sort | Jefferson Antonio Buendía |
| collection | DOAJ |
| description | The evidence available in the pediatric population is limited for making clinical decisions regarding the optimization of tacrolimus (TAC) in pharmacotherapy. The objective of this study was to estimate the frequency of CYP3A5 genetic polymorphisms and their relationship with tacrolimus requirements in the pediatric population. This was a longitudinal cohort study with a two-year follow-up of 77 patients under 18 years old who underwent a liver transplant during the period 2009–2012 at the J.P. Garrahan Pediatric Hospital. Tacrolimus levels from day five up to two years after the transplant were obtained from hospital records of routine therapeutic drug monitoring. The genotyping of CYP3A5 (CYP3A5*1/*3 or *3/*3) was performed in liver biopsies from both the donor and the recipient. The frequency of CYP3A5*1 expression for recipients was 37.1% and 32.2% for donors. Patients who received an expresser organ showed lower Co/dose, especially following 90 days after the surgery. The role of each polymorphism is different according to the number of days after the transplant, and it must be taken into account to optimize the benefits of TAC therapy during the post-transplant induction and maintenance phases. |
| first_indexed | 2024-03-10T16:10:05Z |
| format | Article |
| id | doaj.art-d711fed44214481a9a300ff5879a6a69 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T16:10:05Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d711fed44214481a9a300ff5879a6a692023-11-20T14:36:17ZengMDPI AGPharmaceutics1999-49232020-09-0112989810.3390/pharmaceutics12090898Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver TransplantationJefferson Antonio Buendía0Esteban Halac1Andrea Bosaleh2María T. Garcia de Davila3Oscar Imvertasa4Guillermo Bramuglia5Department of Pharmacology and Toxicology, Faculty of Medicine, University of Antioquia, Medellin 050010, ColombiaLiver Transplant Service, J.P. Garrahan Hospital, Buenos Aires C1245AAM, ArgentinaPathology Service, J.P. Garrahan Hospital, Buenos Aires C1245AAM, ArgentinaPathology Service, J.P. Garrahan Hospital, Buenos Aires C1245AAM, ArgentinaLiver Transplant Service, J.P. Garrahan Hospital, Buenos Aires C1245AAM, ArgentinaFaculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires C1113, ArgentinaThe evidence available in the pediatric population is limited for making clinical decisions regarding the optimization of tacrolimus (TAC) in pharmacotherapy. The objective of this study was to estimate the frequency of CYP3A5 genetic polymorphisms and their relationship with tacrolimus requirements in the pediatric population. This was a longitudinal cohort study with a two-year follow-up of 77 patients under 18 years old who underwent a liver transplant during the period 2009–2012 at the J.P. Garrahan Pediatric Hospital. Tacrolimus levels from day five up to two years after the transplant were obtained from hospital records of routine therapeutic drug monitoring. The genotyping of CYP3A5 (CYP3A5*1/*3 or *3/*3) was performed in liver biopsies from both the donor and the recipient. The frequency of CYP3A5*1 expression for recipients was 37.1% and 32.2% for donors. Patients who received an expresser organ showed lower Co/dose, especially following 90 days after the surgery. The role of each polymorphism is different according to the number of days after the transplant, and it must be taken into account to optimize the benefits of TAC therapy during the post-transplant induction and maintenance phases.https://www.mdpi.com/1999-4923/12/9/898tacrolimusCYP3A5liver transplantpharmacokinetics |
| spellingShingle | Jefferson Antonio Buendía Esteban Halac Andrea Bosaleh María T. Garcia de Davila Oscar Imvertasa Guillermo Bramuglia Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation Pharmaceutics tacrolimus CYP3A5 liver transplant pharmacokinetics |
| title | Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation |
| title_full | Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation |
| title_fullStr | Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation |
| title_full_unstemmed | Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation |
| title_short | Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation |
| title_sort | frequency of cyp3a5 genetic polymorphisms and tacrolimus pharmacokinetics in pediatric liver transplantation |
| topic | tacrolimus CYP3A5 liver transplant pharmacokinetics |
| url | https://www.mdpi.com/1999-4923/12/9/898 |
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