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Quantitative Pharmacology
An Introduction to Integrative Pharmacokinetic-Pharmacodynamic Analysis

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Main description:

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 Pharmacology
The 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 view
What 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 binding
What 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 dependencies
What 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 equilibria
What 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 response
What 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 scaling
When 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

Symbols and their definitions


ISBN-13: 9781466560314
Publisher: Swedish Pharmaceutical Press
Publication date: June, 2012
Pages: 264
Weight: 816g
Availability: Contact supplier
Subcategories: Pharmacology


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