Quantitative Pharmacology (inbunden)
Format
Inbunden (Hardback)
Språk
Engelska
Antal sidor
264
Utgivningsdatum
2012-05-07
Förlag
Swedish Pharmaceutical Press
Illustratör/Fotograf
170 colour illustrations 25 black & white illustrations
Illustrationer
170 Illustrations, color; 25 Illustrations, black and white
Dimensioner
247 x 171 x 25 mm
Vikt
825 g
Antal komponenter
1
ISBN
9781466560314
Quantitative Pharmacology (inbunden)

Quantitative Pharmacology

An Introduction to Integrative Pharmacokinetic-Pharmacodynamic Analysis

Inbunden Engelska, 2012-05-07
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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
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"... 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

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Övrig information

Johan Gabrielsson has been Senior Principal Scientist at AstraZeneca R&D Moelndal. 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, Moelndal. 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, Umea 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.

Innehållsförteckning

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