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罗马尼亚肾移植受者中CYP3A4和CYP3A5的单核苷酸多态性:单中心经验中其对他克莫司药代动力学的影响

Single Nucleotide Polymorphisms of CYP3A4 and CYP3A5 in Romanian Kidney Transplant Recipients: Effect on Tacrolimus Pharmacokinetics in a Single-Center Experience.

作者信息

Rotarescu Corina Andreea, Maruntelu Ion, Rotarescu Ion, Constantinescu Alexandra-Elena, Constantinescu Ileana

机构信息

Immunology and Transplant Immunology, Carol Davila University of Medicine and Pharmacy, 258 Fundeni Avenue, 022328 Bucharest, Romania.

Centre of Immunogenetics and Virology, Fundeni Clinical Institute, 258 Fundeni Avenue, 022328 Bucharest, Romania.

出版信息

J Clin Med. 2024 Mar 28;13(7):1968. doi: 10.3390/jcm13071968.

Abstract

: This study examines the impact of CYP3A4 and CYP 3A5 genotypes on tacrolimus (Tac) pharmacokinetics in Romanian kidney transplanted patients. We included 112 kidney recipients genotyped for CYP3A53, CYP3A41.001, and CYP3A422. Patients were categorized into poor, intermediate, rapid, and ultra-rapid metabolizers based on the functional defects linked to CYP3A variants. Predominantly male (63.4%) with an average age of 40.58 years, the cohort exhibited a high prevalence of the CYP3A41/1 (86.6%) and CYP3A53/3 (77.7%) genotypes. CYP3A41.001 and CYP3A51 alleles significantly influenced the Tac concentration-to-dose (C0/D) ratio in various post-transplant periods, while the CYP3A422 allele showed no such effect ( = 0.016, < 0.001). Stepwise regression highlighted the CYP3A4*1.001's impact in early post-transplant phases, with hematocrit and age also influencing Tac variability. : The study indicates a complex interaction of CYP3A4 and CYP3A5 genotypes on Tac metabolism, suggesting the necessity for personalized medication approaches based on genetic profiling in kidney transplant recipients.

摘要

本研究考察了CYP3A4和CYP 3A5基因多态性对罗马尼亚肾移植患者他克莫司(Tac)药代动力学的影响。我们纳入了112例肾移植受者,对其进行CYP3A53、CYP3A41.001和CYP3A422基因分型。根据与CYP3A变异相关的功能缺陷,将患者分为慢代谢型、中间代谢型、快代谢型和超快代谢型。该队列中男性占主导(63.4%),平均年龄为40.58岁,CYP3A41/1(86.6%)和CYP3A53/3(77.7%)基因型的患病率较高。CYP3A41.001和CYP3A51等位基因在移植后的不同时期对他克莫司的浓度-剂量(C0/D)比值有显著影响,而CYP3A422等位基因则无此作用(P = 0.016,P < 0.001)。逐步回归分析突出了CYP3A4*1.001在移植后早期阶段的影响,同时血细胞比容和年龄也影响他克莫司的变异性。:该研究表明CYP3A4和CYP3A5基因多态性在他克莫司代谢方面存在复杂的相互作用,提示在肾移植受者中基于基因谱进行个性化用药的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1693/11012255/5b2658cc212f/jcm-13-01968-g001.jpg

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