Transl Clin Pharmacol.  2019 Mar;27(1):19-23. 10.12793/tcp.2019.27.1.19.

Evolving role of modeling and simulation in drug development

• Lim HS

• KMID: 2442242
• DOI: http://doi.org/10.12793/tcp.2019.27.1.19

Abstract

Pharmacokinetic-pharmacodynamic model is a kind of language that quantitatively describes the drug-related outcomes in the form of mathematical formula. Various outcomes can be subjected to modeling analysis if they can be expressed in numbers. Empirical models have been widely and successfully applied in drug development and research. However, a more competitive drug development environment requires more accurate and predictive models in the early stages of drug development. Accordingly, the subjects of PK-PD modeling have been extended from clinical data to preclinical and in vitro data in the discovery stage. More mechanistic and predictive models, such as physiologically based pharmacokinetic and quantitative system-based pharmacology models, are being increasingly used owing to the growing need to characterize drugs more accurately at the earliest. This tutorial briefly introduces the essential concepts of PK-PD modeling and simulation and describes the recent changing roles of PK-PD model for application in novel drug development process.

Keyword

Language; Mathematical formula; Pharmacokinetic-pharmacodynamic model; Predictive model

MeSH Terms

In Vitro Techniques
Pharmacology

Figure

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  Figure 1 Pharmacokinetic-pharmacodynamic model as a platform on which different types of data from various sources of the drug development process can be integrated into useful information.

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  Figure 2 Integrative models encompassing the whole mechanistic processes of drug action.

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  Figure 3 Differences in optimal doses between Monte-Carlo simulation and deterministic simulation for efficacy and toxicity versus dose curves.

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  Figure 4 Diagram of whole-body physiologically based pharmacokinetic (WB-PBPK) model. †Black solid and dotted lines indicate blood flow and lymphatic flow, respectively; gray dotted line indicates clearance usually in small molecules.

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