Nikola Stefanović, Katarina Danković, Tatjana Cvetković, Stevan Vujić, Ivan Pavlović, Tatjana Jevtović-Stoimenov, Branka Mitić, Radmila Veličković-Radovanović
{"title":"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。","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":"<p><p><b>Introduction:</b> 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.<b>Aim:</b> 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 (C<sub>0</sub>/D) in various post-transplantation periods.<b>Materials & methods:</b> IL-6 (-174G > C), IL-10 (-1082G > A, -819C > T and -592C > A) genotype, Tac daily dose, C<sub>0</sub>, C<sub>0</sub>/D and intrapatient variability data were collected from 113 patients.<b>Results:</b> 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.<b>Conclusion:</b> This study provides valuable insights regarding the individualized adjustment of Tac treatment in various post-transplantation periods.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"315-327"},"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":"{\"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\":\"<p><p><b>Introduction:</b> 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.<b>Aim:</b> 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 (C<sub>0</sub>/D) in various post-transplantation periods.<b>Materials & methods:</b> IL-6 (-174G > C), IL-10 (-1082G > A, -819C > T and -592C > A) genotype, Tac daily dose, C<sub>0</sub>, C<sub>0</sub>/D and intrapatient variability data were collected from 113 patients.<b>Results:</b> 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.<b>Conclusion:</b> This study provides valuable insights regarding the individualized adjustment of Tac treatment in various post-transplantation periods.</p>\",\"PeriodicalId\":20018,\"journal\":{\"name\":\"Pharmacogenomics\",\"volume\":\" \",\"pages\":\"315-327\"},\"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}","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}
Impact of IL-6 and IL-10 genotypes on tacrolimus dose requirements in kidney transplant recipients: Monte Carlo analysis.
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
