翻译PK/PD：从药物组合的性能和影响的回顾性分析。

IF 6.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Discovery Today Pub Date : 2025-07-01 DOI:10.1016/j.drudis.2025.104417

Rasmus Jansson-Löfmark , Markus Fridén , Lassina Badolo , Christine Ahlström , Ian Gurrell , Menelas N. Pangalos , Rhys DO Jones

{"title":"翻译PK/PD：从药物组合的性能和影响的回顾性分析。","authors":"Rasmus Jansson-Löfmark , Markus Fridén , Lassina Badolo , Christine Ahlström , Ian Gurrell , Menelas N. Pangalos , Rhys DO Jones","doi":"10.1016/j.drudis.2025.104417","DOIUrl":null,"url":null,"abstract":"<div><div>Attrition in drug development continues to be dominated by failure in clinical mid-stage proof-of-concept studies. Successfully demonstrating proof-of-mechanism (PoM) has been reported to be a key factor to improve clinical success. Accurate prediction and testing of PoM are crucial. This analysis of AstraZeneca’s portfolio assesses the role of translational PK/PD modelling in predicting clinical PoM. It has found that 83% of compounds had drug exposure–response within a threefold prediction accuracy. Notably, projects with robust PK/PD packages achieved an 85% success rate in PoM, compared with 33% for those with basic packages. This highlights how translational PK/PD modelling can significantly enhance success rates for drugs entering clinical trials.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 7","pages":"Article 104417"},"PeriodicalIF":6.5000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Translational PK/PD: a retrospective analysis of performance and impact from a drug portfolio\",\"authors\":\"Rasmus Jansson-Löfmark , Markus Fridén , Lassina Badolo , Christine Ahlström , Ian Gurrell , Menelas N. Pangalos , Rhys DO Jones\",\"doi\":\"10.1016/j.drudis.2025.104417\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Attrition in drug development continues to be dominated by failure in clinical mid-stage proof-of-concept studies. Successfully demonstrating proof-of-mechanism (PoM) has been reported to be a key factor to improve clinical success. Accurate prediction and testing of PoM are crucial. This analysis of AstraZeneca’s portfolio assesses the role of translational PK/PD modelling in predicting clinical PoM. It has found that 83% of compounds had drug exposure–response within a threefold prediction accuracy. Notably, projects with robust PK/PD packages achieved an 85% success rate in PoM, compared with 33% for those with basic packages. This highlights how translational PK/PD modelling can significantly enhance success rates for drugs entering clinical trials.</div></div>\",\"PeriodicalId\":301,\"journal\":{\"name\":\"Drug Discovery Today\",\"volume\":\"30 7\",\"pages\":\"Article 104417\"},\"PeriodicalIF\":6.5000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Discovery Today\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1359644625001308\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Discovery Today","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1359644625001308","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

摘要

药物开发中的损耗仍然主要是临床中期概念验证研究的失败。据报道，成功展示机制证明（PoM）是提高临床成功的关键因素。准确预测和测试PoM是至关重要的。本文分析了阿斯利康的产品组合，评估了转化PK/PD模型在预测临床PoM中的作用。它发现83%的化合物具有药物暴露反应，预测精度达到三倍。值得注意的是，拥有强大的PK/PD包的项目在PoM中获得了85%的成功率，而那些拥有基本包的项目只有33%的成功率。这凸显了转化PK/PD模型如何显著提高药物进入临床试验的成功率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Translational PK/PD: a retrospective analysis of performance and impact from a drug portfolio

Attrition in drug development continues to be dominated by failure in clinical mid-stage proof-of-concept studies. Successfully demonstrating proof-of-mechanism (PoM) has been reported to be a key factor to improve clinical success. Accurate prediction and testing of PoM are crucial. This analysis of AstraZeneca’s portfolio assesses the role of translational PK/PD modelling in predicting clinical PoM. It has found that 83% of compounds had drug exposure–response within a threefold prediction accuracy. Notably, projects with robust PK/PD packages achieved an 85% success rate in PoM, compared with 33% for those with basic packages. This highlights how translational PK/PD modelling can significantly enhance success rates for drugs entering clinical trials.

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

Drug Discovery Today 医学-药学

CiteScore

14.80

自引率

2.70%

发文量

293

审稿时长

6 months

期刊介绍： Drug Discovery Today delivers informed and highly current reviews for the discovery community. The magazine addresses not only the rapid scientific developments in drug discovery associated technologies but also the management, commercial and regulatory issues that increasingly play a part in how R&D is planned, structured and executed. Features include comment by international experts, news and analysis of important developments, reviews of key scientific and strategic issues, overviews of recent progress in specific therapeutic areas and conference reports.