Effects of CYP3A5 Genotype on Tacrolimus Pharmacokinetics and Graft-versus-Host Disease Incidence in Allogeneic Hematopoietic Stem Cell Transplantation
Autor: | Daniel N. Marco, Mònica Molina, Ana-María Guio, Judit Julian, Virginia Fortuna, Virginia-Lucila Fabregat-Zaragoza, María-Queralt Salas, Inés Monge-Escartín, Gisela Riu-Viladoms, Esther Carcelero, Joan Ramón Roma, Noemí Llobet, Jordi Arcarons, María Suárez-Lledó, Laura Rosiñol, Francesc Fernández-Avilés, Montserrat Rovira, Mercè Brunet, Carmen Martínez |
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Jazyk: | angličtina |
Rok vydání: | 2024 |
Předmět: | |
Zdroj: | Pharmaceuticals, Vol 17, Iss 5, p 553 (2024) |
Druh dokumentu: | article |
ISSN: | 17050553 1424-8247 |
DOI: | 10.3390/ph17050553 |
Popis: | Tacrolimus (Tac) is pivotal in preventing acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT). It has been reported that genetic factors, including CYP3A5*3 and CYP3A4*22 polymorphisms, have an impact on Tac metabolism, dose requirement, and response to Tac. There is limited information regarding this topic in alloHSCT. The CYP3A5 genotype and a low Tac trough concentration/dose ratio (Tac C0/D ratio) can be used to identify fast metabolizers and predict the required Tac dose to achieve target concentrations earlier. We examined 62 Caucasian alloHSCT recipients with a fast metabolizer phenotype (C0/dose ratio ≤ 1.5 ng/mL/mg), assessing CYP3A5 genotypes and acute GVHD incidence. Forty-nine patients (79%) were poor metabolizers (2 copies of the variant *3 allele) and 13 (21%) were CYP3A5 expressers (CYP3A5*1/*1 or CYP3A5*1/*3 genotypes). CYP3A5 expressers had lower C0 at 48 h (3.7 vs. 6.2 ng/mL, p = 0.03) and at 7 days (8.6 vs. 11.4 ng/mL, p = 0.04) after Tac initiation, tended to take longer to reach Tac therapeutic range (11.8 vs. 8.9 days, p = 0.16), and had higher incidence of both global (92.3% vs. 38.8%, p < 0.001) and grade II-IV acute GVHD (61.5% vs. 24.5%, p = 0.008). These results support the adoption of preemptive pharmacogenetic testing to better predict individual Tac initial dose, helping to achieve the therapeutic range and reducing the risk of acute GVHD earlier. |
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