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Quantitative Pharmacology

Quantitative Pharmacology
Quantitative Pharmacology
  • Συγγραφείς: MD ,  Joel Stein
  • ISBN: 9781466560314
  • Εκδότης: CRC PRESS
  • Σελίδες: 264
  • Έτος Έκδοσης: 2012
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PKPD awareness is vital if we are to attempt to relate preclinical results to the acute and long term consequences in humans. The debate on whether preclinical findings can be translated to the human usage is still engaging scientists across industry, academia and regulatory bodies. Pharmacokinetics (PK) and pharmacodynamics (PD) comprise traditionally distinct disciplines within pharmacology, the study of the interaction of drugs with the body. It is our intention to show that by deliberately, intimately and systematically integrate these disciplines our understanding of drugs and the efficiency and effectiveness of drug discovery and development may be greatly enhanced. The book is therefore written with a broad audience in mind and focuses on concepts. Pharmacologists of all sorts, safety scientists, pharmacokineticists, medicinal chemists, clinicians, statisticians, veterinarians, animal science professionals, project leaders and students of medical, pharmaceutical and veterinary sciences are the primary targets.

This textbook

     

  • Introduces the basics of PK and PD concepts
  • Outlines the implications of integrating PK and PD analysis
  • Introduces the principles behind different biomarkers and inter-species scaling
  • Discusses experimental design of PK, PD and safety studies in non-human species
  • Covers numerous real life Case Studies from the drug discovery arena

Introduction - What is PK/PD and Quantitative PharmacologyThe scope of pharmacokinetics and pharmacodynamics

 

The basic tools of pharmacokinetics and pharmacodynamics

Quantitative pharmacology

Drug discovery and development

Principles of kinetics from a pharmacodynamic point of viewWhat is this chapter about?

 

Essential pharmacokinetic concepts and relationships

Basic principles of compartmental modelling

One-Compartment Models

Constant rate infusion

Integration of clearance and volume

Extravascular administration

Extent of absorption - bioavailability

Accumulation and time to steady-state

Dose-rate and unbound clearance determines free concentration

Multi-Compartment Models

Active metabolites

How is PK and PD integrated?

Principles of plasma protein bindingWhat is this chapter about?

 

Plasma protein binding - General implications

In vitro (closed) versus in vivo (open) systems

Impact of free fraction on PK and PD properties

How is information about PPB integrated with PD?

Principles of dose, time and flow dependenciesWhat is this chapter about?

 

Capacity-dependent kinetics

Time-dependent kinetics

Combining Capacity, Flow and Time-dependent kinetics

Target mediated drug disposition (TMDD)

How is nonlinear drug disposition integrated with PD?

Principles of rapid concentration-response equilibriaWhat is this chapter about?

 

Why concentration-response instead of dose-response?

Multiple dose pharmacodynamics

Linear concentration-response relationship - case example

Exponential concentration-response relationship

Hill versus log-linear models

Michaelis-Menten type of binding model

Case Study example: Analysis of brain occupancy and exposure data of several species

Summary and discussion of concentration response relationships

Time delays between plasma concentration and responseWhat is this chapter about?

 

Time delays observed as hysteresis

Delays caused by distributional processes

Delays caused by turnover

Delays caused by slow receptor on/offset

Comparisons of the link-, turnover and receptor on/off models

Principles of inter-species scalingWhen and why do we extrapolate data across species?

 

What is allometry and allometric equations?

The elementary Dedrick plot

Examples of allometric plots

Time scales differ between different species

Physiological variables of 11 animal species and man

Allometric scaling of turnover parameters

General conclusions

Dose nomogram and scaling of pharmacodynamic parameters

Principles of candidate drug selection for a first time in man study: Allometry, dose-nomogram and safety margin

Bibliography

Symbols and their definitions

Index

 

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