Topic
Physiologically based pharmacokinetic modelling
About: Physiologically based pharmacokinetic modelling is a research topic. Over the lifetime, 2166 publications have been published within this topic receiving 53266 citations. The topic is also known as: PBPK model & PBPK models.
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1,286 citations
TL;DR: Improvement in parameter prediction was largely due to the incorporation of distribution processes related to drug ionisation, an issue that is not addressed in earlier equations.
733 citations
TL;DR: Overall improvement in prediction should facilitate the further application of WBPBPK modeling, where time, cost and labor requirements associated with experimentally determining Kpu's have, to a large extent, deterred its application.
638 citations
TL;DR: Specific advances and contemporary challenges with respect to predicting the processes of drug clearance, distribution, and absorption are reviewed, together with the ability to anticipate the quantitative extent of PK-based drug-drug interactions and the impact of age, genetics, disease, and formulation.
Abstract: The application of physiologically-based pharmacokinetic (PBPK) modeling is coming of age in drug development and regulation, reflecting significant advances over the past 10 years in the predictability of key pharmacokinetic (PK) parameters from human in vitro data and in the availability of dedicated software platforms and associated databases. Specific advances and contemporary challenges with respect to predicting the processes of drug clearance, distribution, and absorption are reviewed, together with the ability to anticipate the quantitative extent of PK-based drug-drug interactions and the impact of age, genetics, disease, and formulation. The value of this capability in selecting and designing appropriate clinical studies, its implications for resource-sparing techniques, and a more holistic view of the application of PK across the preclinical/clinical divide are considered. Finally, some attention is given to the positioning of PBPK within the drug development and approval paradigm and its future application in truly personalized medicine.
573 citations
TL;DR: Recent instances of the use of PBPK in decision‐making during regulatory review are reviewed, based on Center for Drug Evaluation and Research reviews of several submissions for investigational new drugs and new drug applications received between July 2008 and June 2010.
Abstract: Physiologically based pharmacokinetic (PBPK) modeling and simulation is a tool that can help predict the pharmacokinetics of drugs in humans and evaluate the effects of intrinsic (e.g., organ dysfunction, age, genetics) and extrinsic (e.g., drug-drug interactions) factors, alone or in combinations, on drug exposure. The use of this tool is increasing at all stages of the drug development process. This report reviews recent instances of the use of PBPK in decision-making during regulatory review. The examples are based on Center for Drug Evaluation and Research reviews of several submissions for investigational new drugs (INDs) and new drug applications (NDAs) received between July 2008 and June 2010. The use of PBPK modeling and simulation facilitated the following types of decisions: the need to conduct specific clinical pharmacology studies, specific study designs, and appropriate labeling language. The report also discusses the challenges encountered when PBPK modeling and simulation were used in these cases and recommends approaches to facilitating full utilization of this tool.
437 citations