评估已发表的人群药代动力学模型,为成人肺移植受者的他克莫司治疗提供参考。

IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
Therapeutic Drug Monitoring Pub Date : 2024-08-01 Epub Date: 2024-05-09 DOI:10.1097/FTD.0000000000001210
Ranita Kirubakaran, Rani M Singh, Jane E Carland, Richard O Day, Sophie L Stocker
{"title":"评估已发表的人群药代动力学模型,为成人肺移植受者的他克莫司治疗提供参考。","authors":"Ranita Kirubakaran, Rani M Singh, Jane E Carland, Richard O Day, Sophie L Stocker","doi":"10.1097/FTD.0000000000001210","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The applicability of currently available tacrolimus population pharmacokinetic models in guiding dosing for lung transplant recipients is unclear. In this study, the predictive performance of relevant tacrolimus population pharmacokinetic models was evaluated for adult lung transplant recipients.</p><p><strong>Methods: </strong>Data from 43 lung transplant recipients (1021 tacrolimus concentrations) administered an immediate-release oral formulation of tacrolimus were used to evaluate the predictive performance of 17 published population pharmacokinetic models for tacrolimus. Data were collected from immediately after transplantation up to 90 days after transplantation. Model performance was evaluated using (1) prediction-based assessments (bias and imprecision) of individual predicted tacrolimus concentrations at the fourth dosing based on 1 to 3 previous dosings and (2) simulation-based assessment (prediction-corrected visual predictive check; pcVPC). Both assessments were stratified based on concomitant azole antifungal use. Model performance was clinically acceptable if the bias was within ±20%, imprecision was ≤20%, and the 95% confidence interval of bias crossed zero.</p><p><strong>Results: </strong>In the presence of concomitant antifungal therapy, no model showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33), and pcVPC plots displayed poor model fit to the data set. However, this fit slightly improved in the absence of azole antifungal use, where 4 models showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33).</p><p><strong>Conclusions: </strong>Although none of the evaluated models were appropriate in guiding tacrolimus dosing in lung transplant recipients receiving concomitant azole antifungal therapy, 4 of these models displayed potential applicability in guiding dosing in recipients not receiving concomitant azole antifungal therapy. However, further model refinement is required before the widespread implementation of such models in clinical practice.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"434-445"},"PeriodicalIF":2.8000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluation of Published Population Pharmacokinetic Models to Inform Tacrolimus Therapy in Adult Lung Transplant Recipients.\",\"authors\":\"Ranita Kirubakaran, Rani M Singh, Jane E Carland, Richard O Day, Sophie L Stocker\",\"doi\":\"10.1097/FTD.0000000000001210\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The applicability of currently available tacrolimus population pharmacokinetic models in guiding dosing for lung transplant recipients is unclear. In this study, the predictive performance of relevant tacrolimus population pharmacokinetic models was evaluated for adult lung transplant recipients.</p><p><strong>Methods: </strong>Data from 43 lung transplant recipients (1021 tacrolimus concentrations) administered an immediate-release oral formulation of tacrolimus were used to evaluate the predictive performance of 17 published population pharmacokinetic models for tacrolimus. Data were collected from immediately after transplantation up to 90 days after transplantation. Model performance was evaluated using (1) prediction-based assessments (bias and imprecision) of individual predicted tacrolimus concentrations at the fourth dosing based on 1 to 3 previous dosings and (2) simulation-based assessment (prediction-corrected visual predictive check; pcVPC). Both assessments were stratified based on concomitant azole antifungal use. Model performance was clinically acceptable if the bias was within ±20%, imprecision was ≤20%, and the 95% confidence interval of bias crossed zero.</p><p><strong>Results: </strong>In the presence of concomitant antifungal therapy, no model showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33), and pcVPC plots displayed poor model fit to the data set. However, this fit slightly improved in the absence of azole antifungal use, where 4 models showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33).</p><p><strong>Conclusions: </strong>Although none of the evaluated models were appropriate in guiding tacrolimus dosing in lung transplant recipients receiving concomitant azole antifungal therapy, 4 of these models displayed potential applicability in guiding dosing in recipients not receiving concomitant azole antifungal therapy. However, further model refinement is required before the widespread implementation of such models in clinical practice.</p>\",\"PeriodicalId\":23052,\"journal\":{\"name\":\"Therapeutic Drug Monitoring\",\"volume\":\" \",\"pages\":\"434-445\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Drug Monitoring\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/FTD.0000000000001210\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/9 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Drug Monitoring","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/FTD.0000000000001210","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/9 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:目前可用的他克莫司群体药代动力学模型在指导肺移植受者用药方面的适用性尚不明确。本研究评估了相关他克莫司群体药代动力学模型对成年肺移植受者的预测性能:方法:43 名肺部移植受者(1021 个他克莫司浓度)服用了他克莫司速释口服制剂的数据被用来评估 17 个已发表的他克莫司群体药代动力学模型的预测性能。数据收集时间为移植后即刻至移植后 90 天。评估模型性能的方法包括:(1) 基于预测的评估(偏差和不精确性),即根据之前的 1 至 3 次用药对第四次用药时单个药物的他克莫司浓度进行预测;(2) 基于模拟的评估(预测校正视觉预测检查;pcVPC)。两种评估均根据同时使用唑类抗真菌药物的情况进行分层。如果偏差在±20%以内,不精确度≤20%,且偏差的95%置信区间为零,则模型性能在临床上是可接受的:结果:在同时接受抗真菌治疗的情况下,在预测第四次给药时他克莫司的浓度(n = 33)时,没有任何模型显示出可接受的性能,pcVPC图显示模型与数据集的拟合度较差。然而,在不使用唑类抗真菌药物的情况下,这种拟合情况略有改善,有 4 个模型在预测第四次给药时的他克莫司浓度时表现出了可接受的性能(n = 33):结论:尽管所评估的模型中没有一个适合用于指导同时接受唑类抗真菌治疗的肺移植受者的他克莫司剂量,但其中 4 个模型显示出潜在的适用性,可用于指导未同时接受唑类抗真菌治疗的受者的剂量。不过,在临床实践中广泛应用这些模型之前,还需要进一步完善模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluation of Published Population Pharmacokinetic Models to Inform Tacrolimus Therapy in Adult Lung Transplant Recipients.

Background: The applicability of currently available tacrolimus population pharmacokinetic models in guiding dosing for lung transplant recipients is unclear. In this study, the predictive performance of relevant tacrolimus population pharmacokinetic models was evaluated for adult lung transplant recipients.

Methods: Data from 43 lung transplant recipients (1021 tacrolimus concentrations) administered an immediate-release oral formulation of tacrolimus were used to evaluate the predictive performance of 17 published population pharmacokinetic models for tacrolimus. Data were collected from immediately after transplantation up to 90 days after transplantation. Model performance was evaluated using (1) prediction-based assessments (bias and imprecision) of individual predicted tacrolimus concentrations at the fourth dosing based on 1 to 3 previous dosings and (2) simulation-based assessment (prediction-corrected visual predictive check; pcVPC). Both assessments were stratified based on concomitant azole antifungal use. Model performance was clinically acceptable if the bias was within ±20%, imprecision was ≤20%, and the 95% confidence interval of bias crossed zero.

Results: In the presence of concomitant antifungal therapy, no model showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33), and pcVPC plots displayed poor model fit to the data set. However, this fit slightly improved in the absence of azole antifungal use, where 4 models showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33).

Conclusions: Although none of the evaluated models were appropriate in guiding tacrolimus dosing in lung transplant recipients receiving concomitant azole antifungal therapy, 4 of these models displayed potential applicability in guiding dosing in recipients not receiving concomitant azole antifungal therapy. However, further model refinement is required before the widespread implementation of such models in clinical practice.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Therapeutic Drug Monitoring
Therapeutic Drug Monitoring 医学-毒理学
CiteScore
5.00
自引率
8.00%
发文量
213
审稿时长
4-8 weeks
期刊介绍: Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信