Moving from Basic Toward Systems Pharmacodynamic Models

doi:10.1002/jps.23590

Journal of Pharmaceutical Sciences

Volume 102, Issue 9, September 2013, Pages 2930-2940

https://doi.org/10.1002/jps.23590 Get rights and content

ABSTRACT

Building upon many classical foundations of pharmacology, a diverse array of mechanistic pharmacokinetic-pharmacodynamic (PK/PD) models have emerged based on mechanisms of drug action and primary rate-limiting or turnover processes in physiology. An array of basic models can be extended to handle various complexities including tolerance and can readily be employed as building blocks in assembling enhanced PK/PD or small systems models. Our corticosteroid models demonstrate these concepts as well as elements of horizontal and vertical integration of molecular to whole-body processes. The potential advantages and challenges in moving PK/PD toward systems models are described.

Section snippets

INTRODUCTION

The areas of pharmacokinetics and pharmacodynamics (PK/PD) have evolved from a long history of appreciation of basic pharmacological principles mostly applied to static or in vitro systems. An array of simple PK/PD models for the time course of in vivo drug effects have evolved to the present era of use of extended or enhanced PK/PD models and small-to-large systems models to capture drug actions at various levels of biological organization. This overview will describe the various arenas that

ACKNOWLEDGMENTS

This work was supported by NIH grants GM 24211 and 57980. The author appreciates the many contributions of his esteemed colleagues, collaborators, fellows, students, and technicians for those aspects of this work that is cited herein as well as forming the basis for his PKPD modeling efforts over the course of his career. The assistance of Katherine Majewski from the National Library of Medicine is also appreciated. Our efforts were part of the activities of the UB Center of Excellence in

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: This article is partly based on presentations given at the American College of Clinical Pharmacology, September 2012, upon my receipt of the Distinguished Investigator Award and at the American Society of Clinical Pharmacology and Therapeutics, March 2013, upon my receipt of the Sheiner-Beal Pharmacometrics Award. Journal of Pharmaceutical Sciences, Vol. 102, 2930–2940 (2013)

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ReviewsMoving from Basic Toward Systems Pharmacodynamic Models

ABSTRACT

Section snippets

INTRODUCTION

ACKNOWLEDGMENTS

J Theor Biol

J Pharm Sci

J Pharm. Sci

J Pharm Sci

Bone

Kinetics of pharmacologic effects

Clin Pharmacol Ther

Model-based drug development

Clin Pharmacol Ther

Opportunities for integration of pharmacokinetics, pharmacodynamics, and toxicokinetics in rational drug development

Pharm Res

Optimizing the science of drug development: Opportunities for better candidate selection and accelerated evaluation in humans

J Clin Pharmacol

Impact of pharmacometric reviews on new drug approval and labeling decisions—A survey of 31 new drug applications submitted between 2005 and 2006

Clin Pharmacol Ther

Quantitative disease, drug, and trial models

Annu Rev Pharmacol Toxicol

News from the National Institute of General Medical Sciences: What is training in the pharmacological sciences?

Pharm Res

Quantitative and systems pharmacology in the postgenomic era: New approaches to discovering and understanding therapeutic drugs and mechanisms

NIH support of the emergence of quantitative and systems pharmacology

CPT: Pharmacomet Syst Pharmacol

Development of translational pharmacokinetic-pharmacodynamic models

Clin Pharmacol Ther

Physiologically based pharmacokinetics in drug development and regulatory science

Annu Rev Pharmacol Toxicol

Physiologically based pharmacokinetic (PBPK) model to predict IgG tissue kinetics in wildtype and FcRn-knockout mice

J Pharmacokinet Pharmacodyn

Applications of minimal physiologically based pharmacokinetic models

J Pharmacokin Pharmacodyn

The pharmacology of vascular smooth muscle

Pharmacol Rev

Simultaneous modeling of pharmacokinetics and pharmacodynamics: Application to d-tubocurarine

Clin Pharmacol Ther

Pharmacokinetic/ pharmacodynamic modelling in diabetes

Clin Pharmacokin

Chemotherapeutics: Scientific principles, methods, and results

Lancet

The mode of action of drugs on cells

The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves

J Physiol

Operational models of pharmacological agonism

Proc R Soc Lond B Biol Sci

Pharmacologic analysis of drug-receptor interaction

Reviews
Moving from Basic Toward Systems Pharmacodynamic Models