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 are brought together in one publication.
Non-Clinical Vascular Infusion Technology, Volume I: The Science covers the scientific principles behind the delivery systems, from both physical and physiological standpoints. The book 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. This volume, along with Volume II: The Techniques, provides a foundation of knowledge on infusion technology and its importance for safe clinical use of substances via this route of delivery.
- Identifies and shares best practices for non-clinical vascular infusion
- Presents modern practices and procedures in line with up-to-date equipment development
- Offers recommendations for in-life assessments in order to monitor the success or problems with the vascular infusion delivery
- Makes comparisons with human data in many areas
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
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 masters 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.
"Good science and good welfare go hand in hand. Innovative science and technology can be used to improve animal welfare. Equally, the 3Rs (replacement, refinement and reduction of animals in research) can provide fresh insight and novel approaches to advance science. By sharing data, knowledge and experience on the science behind infusion models and the refinement of the techniques used, there is the potential to have a significant impact on the 3Rs.
Owen Green and Guy Healing have shown the importance of the 3Rs in infusion technology at international meetings and in producing this book. The book will enhance uptake of the latest science behind vascular delivery systems to get better data and help influence decisions around the most appropriate model. It will also contribute to preventing repetition of method development and optimising experiments to answer specific scientific questions with the least impact on animals.
As in other areas of science, the field of infusion technology is constantly evolving. This edition of Non-Clinical Vascular Infusion Technology reviews current developments in the field that will support scientists in putting the 3Rs into practice."
—From the Foreword by Kathryn Chapman, Head of Innovation and Translation, the National Centre for the Replacement, Refinement and Reduction of Animals in Research