Quantitative Pharmacology: An Introduction to Integrative Pharmacokinetic-Pharmacodynamic Analysis, 1st Edition (Hardback) book cover

Quantitative Pharmacology

An Introduction to Integrative Pharmacokinetic-Pharmacodynamic Analysis, 1st Edition

By Johan Gabrielsson, Stephan Hjorth

Swedish Pharmaceutical Press

264 pages | 170 Color Illus. | 25 B/W Illus.

Purchasing Options:$ = USD
Hardback: 9781466560314
pub: 2012-05-07
SAVE ~$31.00
$155.00
$124.00
x

FREE Standard Shipping!

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

Reviews

"… provides very attractive and comprehensive reading for a broad audience—inside as well as outside Pharma—with interest in integrating PK and PD observations for greater understanding of how to connect drug fate and treatment consequences in vivo."

—Professor Arvid Carlsson, Nobel Laureate, Gothenburg University

"I consider the book by Gabrielsson and Hjorth to be very useful for in depth studies by scientists working with drug development and experimentalists in clinical pharmacology. It combines the analysis of effects versus time patterns with kinetic corollaries in a most comprehensive way. Moreover, it is a book of great graphical beauty exceptionally styled with a cover painted by one of the authors."

--Gunnar Alvan MD PhD, Emeritus professor and former Director General of the Swedish Medical Products Agency

Table of Contents

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

Bibliography

Symbols and their definitions

Index

About the Authors

Johan Gabrielsson has been Senior Principal Scientist at AstraZeneca R&D Mölndal. His responsibilities included kinetic/dynamic related project tasks in the CV & GI & CNS & Cancer & Biologics areas. He is author of the textbook ‘Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications’ 4th ed. (2006). He is professor of Integrative Pharmacology at the Swedish Agricultural University in Uppsala, Sweden. He is also academically affiliated with Dept. of Pharmaceutics, Univ. Tennessee and University of Manchester. He has published extensively in the field of pharmacokinetic-pharmacodynamic modeling and reasoning, and has run numerous courses internally and externally in the area of biological data analysis since 1985 in Europe, the US and Asia (>4000 participants) at both the undergraduate and graduate level. His research focuses on modelling different aspects of endogenous turnover, such as functional tolerance and rebound phenomena, physiological limits and target-mediated drug disposition in collaboration with Professor LA Peletier, Leiden University. He has been external examiner on several PhD Theses abroad.

Stephan Hjorth is Principal Scientist at the Bioscience Dept., AstraZeneca R&D, Mölndal. His main responsibilities includes pharmacodynamic-related project tasks in the CV&GI, metabolism, area. Before joining AstraZeneca R&D he spent ~25 years in various positions at the Dept. of Pharmacology, Gothenburg Univ., and latterly as appointed professor at the Dept. of Pharmacology & Clinical Neurosciences, Umeå Univ., doing research and teaching at the undergraduate as well as the graduate level. He has published extensively, mainly in the field of preclinical neuro- and psychopharmacology, and also acted as editor for the Journal of Neural Transmission. He is a member of several national and international scientific societies, has reviewed grant applications to the EU Framework programme and other foreign grant agencies, and been external examiner at several PhD dissertations in Sweden and abroad. His current research primarily focuses on discovery and development of drugs for obesity and appetite control, including efforts towards animal models useful in translational modelling of PK-PD relationships.

Subject Categories

BISAC Subject Codes/Headings:
MED071000
MEDICAL / Pharmacology
SCI086000
SCIENCE / Life Sciences / General