Intravenous infusion is a necessary mode of delivery for many pharmaceuticals currently on the market or undergoing clinical trials. The technique of prolonged intravenous delivery in conscious, free-moving animal models has broadened the opportunity to study and evaluate the safety and efficacy of these therapeutic products. For the first time, the collective sciences involved in the understanding of this mode of drug delivery and the methodologies for carrying it out are brought together in a comprehensive work, Non-Clinical Vascular Infusion Technology, Two Volume Set: Science and Techniques.
Volume I: The Science covers the scientific principles behind the delivery systems, from both physical and physiological standpoints. It addresses body fluid dynamics, describes the scientific processes necessary to understand the various aspects of the physico-chemical issues relating to vascular infusion delivery, and discusses vascular infusion dynamics. It also considers all the essential elements of the preparation of a formulation intended for vascular delivery as well as assessment of compatibility of the formulation with the dosing apparatus.
Volume II: The Techniques builds upon the highly praised Handbook of Pre-Clinical Continuous Intravenous Infusion and provides a current account of the techniques and equipment involved in all the major laboratory animal species for conducting successful vascular infusion studies with xenobiotics. It is organized by species, including all those commonly used in pre-clinical studies: rat, mouse, dog, minipig, large primate, and marmoset. There are also chapters on juvenile studies and reproductive toxicity studies. Each section addresses the selection of the best model, surgical and non-surgical best practices, practical techniques, equipment selection, and commonly encountered background pathologies.
Using a fresh approach, the authors identify best practices to be shared across the industry, and provide guidance on choices for the most acceptable methodologies from an animal welfare perspective. This two-volume set provides a foundation of knowledge on infusion technology and its importance for safe clinical use of substances via this route of delivery.
Table of Contents
Body Fluid Dynamics
Composition and units of measurement
Compartmentalization and Distribution
Movement between Compartments/Exchange
Body Fluid Homeostasis
Summary of Infusion Forces
Vascular Infusion Dynamics
Intravenous Delivery Rates and Volumes
Formulation Considerations, Co-author: Kevin Sooben
Formulation selection strategy
Study design and species/strain
The properties of the compound
Strategies for dealing with poor solubility
Unwanted formulation effects
Strategies for dealing with injection site reactions and haemolysis
Strategies for dealing with poor stability
Prestudy analytical assessments:
Equipment compatibility, Co-author: James Baker
Stability of the formulation with the formulation storage vessel
Choice of material
Haemocompatibility, Co-author: Sophie Hill
Methods of assessing haemocompatibility
Annex: Common excipients and vehicles
Jennifer Sheehan, Duncan Patten and Vasanthi Mowat
Hans van Wijk and Alice J M Fraser
John Cody Resendez and David Rehagen
Christine Copeman and Stephanie Clubb
Peter Glerup, Mikala Skydsgaard and Gitte Jeppesen
Teresa R. Gleason and George A. Parker
Dr. Sven Korte, Dr. Piotr Nowak, Dr. Jörg Luft and Dr. Birgit Niggemann
Owen Green is a toxicologist who has spent nearly 40 years in the preclinical toxicology industry within leading global CROs or as an independent consultant in toxicology to pharmaceutical and chemical sectors. Following his master’s degree in pharmacological biochemistry and Ph.D. studying chronic renal disease, he has spent many years working with and studying the practice of infusion technology in non-clinical toxicology programmes. He is one of the founders and current chairman of the Infusion Technology Organisation. This is an international group set up to share commercial and academic experiences with the technology in order to improve the techniques and scientific understanding for the benefit of the animal models involved and to improve the scientific quality of the data generated.
Guy Healing is an experienced regulatory toxicologist who has worked in pre-clinical pharmaceutical R&D for nearly 20 years, and prior to that in agrochemical R&D and for a global CRO. He obtained a BSc in biochemistry at Cardiff University and his Ph.D. investigating the role of iron and oxygen-derived free radicals in the pathogenesis of renal ischaemic damage while working for the Medical Research Council. Guy is a Fellow of the British Toxicology Society and has been editor of its newsletter as well as a member of the Executive Committee. He has published previously in the area of infusion technology, including the Handbook of Pre-clinical Continuous Intravenous Infusion in 2000.
"This book provides comprehensive, practice-oriented guidelines for scientists who design and perform studies with vascular drug delivery techniques. I highly recommend this book for both new and experienced scientists who plan to work with, or are already working with, vascular infusion techniques. Weighted numerical score: 96 - 4 stars."
—Ivan Laszlo Csanaky, MD, Ph.D, University of Kansas School of Medicine, Kansas City, USA from Doody's Book Reviews™
"Owen Green and Guy Healing have shown the importance of the 3Rs in infusion technology at international meetings and in producing this book."
—From the Foreword by Kathryn Chapman, Head of Innovation and Translation, the National Centre for the Replacement, Refinement and Reduction of Animals in Research
Praise for the First Edition, Handbook of Pre-clinical Continuous Intravenous Infusion
" ... an excellent buy for anyone involved in drug development, risk assessment or within drug licensing agencies and in academic research. ... This book represents a benchmark achievement for this technique ... it will become the standard for many years to come."
—British Toxicology Society Newsletter