Impact of IL-6 and IL-10 genotypes on tacrolimus dose requirements in kidney transplant recipients: Monte Carlo analysis.

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-07-29 DOI:10.1080/14622416.2024.2379227

Nikola Stefanović, Katarina Danković, Tatjana Cvetković, Stevan Vujić, Ivan Pavlović, Tatjana Jevtović-Stoimenov, Branka Mitić, Radmila Veličković-Radovanović

{"title":"Impact of IL-6 and IL-10 genotypes on tacrolimus dose requirements in kidney transplant recipients: Monte Carlo analysis.","authors":"Nikola Stefanović, Katarina Danković, Tatjana Cvetković, Stevan Vujić, Ivan Pavlović, Tatjana Jevtović-Stoimenov, Branka Mitić, Radmila Veličković-Radovanović","doi":"10.1080/14622416.2024.2379227","DOIUrl":null,"url":null,"abstract":"Introduction: IL-6 and IL-10 may affect the activity of cytochrome P450 (CYP) 3A enzymes involved in tacrolimus (Tac) metabolism. Moreover, the effect of IL-6 and IL-10 on Tac pharmacokinetics may differ with respect to the genetic variations in their genes.Aim: To examine the influence of IL-6 and IL-10 gene polymorphisms on Tac dose requirements and exposure over a 5-year period following kidney transplantation. Univariate and standard multivariate linear regression and Monte Carlo analysis were performed to investigate potential covariates influencing Tac dose-adjusted trough concentration (C0/D) in various post-transplantation periods.Materials & methods: IL-6 (-174G > C), IL-10 (-1082G > A, -819C > T and -592C > A) genotype, Tac daily dose, C0, C0/D and intrapatient variability data were collected from 113 patients.Results: Multivariate regression analysis and accompanied Monte Carlo simulation underscore the importance of considering IL-6 -174G > C and IL-10 -1082G > A gene polymorphisms, alongside Tac metabolic phenotype and post-transplantation period, when tailoring Tac dosage regimen.Conclusion: This study provides valuable insights regarding the individualized adjustment of Tac treatment in various post-transplantation periods.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404698/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14622416.2024.2379227","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/29 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: IL-6 and IL-10 may affect the activity of cytochrome P450 (CYP) 3A enzymes involved in tacrolimus (Tac) metabolism. Moreover, the effect of IL-6 and IL-10 on Tac pharmacokinetics may differ with respect to the genetic variations in their genes.Aim: To examine the influence of IL-6 and IL-10 gene polymorphisms on Tac dose requirements and exposure over a 5-year period following kidney transplantation. Univariate and standard multivariate linear regression and Monte Carlo analysis were performed to investigate potential covariates influencing Tac dose-adjusted trough concentration (C₀/D) in various post-transplantation periods.Materials & methods: IL-6 (-174G > C), IL-10 (-1082G > A, -819C > T and -592C > A) genotype, Tac daily dose, C₀, C₀/D and intrapatient variability data were collected from 113 patients.Results: Multivariate regression analysis and accompanied Monte Carlo simulation underscore the importance of considering IL-6 -174G > C and IL-10 -1082G > A gene polymorphisms, alongside Tac metabolic phenotype and post-transplantation period, when tailoring Tac dosage regimen.Conclusion: This study provides valuable insights regarding the individualized adjustment of Tac treatment in various post-transplantation periods.

查看原文本刊更多论文

IL-6和IL-10基因型对肾移植受者他克莫司剂量需求的影响：蒙特卡罗分析。

引言IL-6和IL-10可能会影响参与他克莫司（Tac）代谢的细胞色素P450（CYP）3A酶的活性。此外，IL-6 和 IL-10 对他克莫司药代动力学的影响可能因其基因的遗传变异而不同。目的：研究IL-6和IL-10基因多态性对肾移植后5年内Tac剂量需求和暴露的影响。进行单变量和标准多变量线性回归及蒙特卡罗分析，以研究影响移植后不同时期 Tac 剂量调整后谷浓度（C0/D）的潜在协变量。材料与方法：收集了113例患者的IL-6（-174G > C）、IL-10（-1082G > A、-819C > T和-592C > A）基因型、Tac日剂量、C0、C0/D和患者间变异性数据。研究结果多变量回归分析和蒙特卡洛模拟强调了在定制 Tac 剂量方案时考虑 IL-6 -174G > C 和 IL-10 -1082G > A 基因多态性以及 Tac 代谢表型和移植后时期的重要性。结论本研究就移植后不同时期 Tac 治疗的个体化调整提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.