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.
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http://dx.doi.org/10.3390/pharmaceutics12090898 | DOI Listing |
Sci Rep
December 2024
National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand.
Inter-individual variability in drug responses is significantly influenced by genetic factors, underscoring the importance of population-specific pharmacogenomic studies to optimize clinical outcomes. In this study, we analyzed whole genome sequencing data from 949 unrelated Thai individuals and conducted an in-depth analysis of 3239 genes involved in drug pharmacokinetics, pharmacodynamics, or immune-mediated adverse drug reactions. We identified 43 single nucleotide polymorphisms (SNPs), 134 diplotypes, and 15 human leukocyte antigen (HLA) alleles, all with moderate to high clinical significance.
View Article and Find Full Text PDFPathol Res Pract
December 2024
Department of General Biology, Center of Biological Sciences, State University of Londrina (UEL), Londrina 86057-970, Brazil. Electronic address:
Biomarkers that identify tumors with better/worse prognosis can help reduce treatment costs and contribute to patient survival. In urothelial bladder cancer (UBC), accurate prediction of recurrence and progression is essential to inform therapeutic management. Herein, we explore the role of genetic variants of xenobiotic metabolic pathways in UBC susceptibility and prognosis.
View Article and Find Full Text PDFJ Chem Theory Comput
December 2024
Laboratoire de Biologie et Pharmacologie Appliquée (LBPA), UMR 8113, CNRS, École Normale Supérieure Paris-Saclay, Gif-sur-Yvette 91190, France.
Proteins are dynamic entities that adopt diverse conformations, which play a pivotal role in their function. Understanding these conformations is essential, and protein collective motions, particularly those captured by normal mode (NM) and their linear combinations, provide a robust means for conformational sampling. This work introduces a novel approach to obtaining a uniformly oriented set of a given number of lowest frequency NM combined vectors and generating harmonically equidistant restrained structures along them.
View Article and Find Full Text PDFYakugaku Zasshi
December 2024
Department of Pharmacy, University of Miyazaki Hospital.
Tacrolimus is widely recognized as an anti-rejection agent due to its immunosuppressive characteristics. It binds to the immunophilin FK506-binding protein (FKBP) and thus to calcineurin, and inhibits its activity. Tacrolimus' therapeutic concentration range in blood is narrow, and its pharmacokinetics are highly variable among individuals.
View Article and Find Full Text PDFEur J Med Res
November 2024
Cardiology Department, Faculty of Medicine, Helwan University, Helwan City, 11795, Cairo, Egypt.
Background: A single nucleotide polymorphism (SNP) is a variation in the DNA sequence that results from the alteration of a single nucleotide in the genome. Atorvastatin is used to treat hypercholesterolemia. It belongs to a class of drugs called statins, which lower elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C).
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