超越 CL 和 VSS：人体药代动力学预测的综合方法。

IF 6.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Discovery Today Pub Date : 2024-11-08 DOI:10.1016/j.drudis.2024.104238

Anneke Himstedt , Hermann Rapp , Peter Stopfer , Ralf Lotz , Stefan Scheuerer , Thomas Arnhold , Achim Sauer , Jens Markus Borghardt

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引用次数: 0

摘要

人体药代动力学（PK）是临床候选药物筛选的一项重要任务，本文全面考察了与预测人体药代动力学相关的过程。通过系统地将体外吸收、分布、代谢和排泄（ADME）以及体内 PK 数据与专家判断相结合，该研究对勃林格殷格翰公司新化学实体（NCE）产品组合中的 40 种口服化合物进行了高质量的人体 PK 预测。总之，文章利用最先进的方法，对预测全浓度-时间曲线的结构化流程进行了详细评估和指导，使其超越了单一参数预测。此外，文章还讨论了未来的挑战和改进，旨在为从事药物代谢、PK 和药效学研究的科学家提供有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Beyond CL and VSS: A comprehensive approach to human pharmacokinetic predictions

This article presents a comprehensive examination of processes related to the prediction of human pharmacokinetics (PK), a crucial task of clinical drug candidate selection. By systematically incorporating in vitro absorption, distribution, metabolism and excretion (ADME) and in vivo PK data with expert judgement, the study achieves high-quality human PK predictions for 40 orally administered compounds from Boehringer Ingelheim’s new chemical entity (NCE) portfolio. Overall, the article provides a detailed evaluation of and guidance for a structured process to predict full concentration–time profiles beyond single-parameter predictions, using state-of-the-art methodologies. Furthermore, it discusses future challenges and improvements, and aims to provide valuable insights for scientists working in drug metabolism and PK (DMPK) or PK/pharmacodynamics (PK/PD) modelling.

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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.