Preface

The original aim of this book was to produce a useable handbook on drug transporters, one that would be in the offices and laboratories of scientists from every discipline as a source of reference, be it on the fundamental aspects, or some of the newer, emerging disciplines of transporter science. To date, there are no books that specifically address this aspect, concentrating instead on in-depth reviews and discussions of particular topics. We hope that this book, divided into two volumes, will fill the current gap by encompassing a review of the available knowledge, techniques and tools within the transporter sciences as they relate to drug disposition and pharmacokinetics. It brings together the collective knowledge of over 200 years of expertise from a network of scientists from a variety of backgrounds and countries, with a particular focus being given to the role of membrane transporters in drug absorption, distribution, metabolism and elimination (ADME), and their impact on drug safety and drug efficacy. Since the book is intended for both newcomers and established scientists, coverage is given to almost all areas of the field, together with links to databases, references and reviews for the interested reader.

For ease of reference, the book as a whole is divided into four sections, with each section describing the current (2016) situation in the field of drug transporters. Given the extensive nature of the topics chosen, and our wish to include as many subject areas as possible, it has been necessary to divide the book into two separate volumes, with the first volume concentrating primarily on the theory and practice of those drug transporters currently used within the pharmaceutical industry and the second volume outlining some of the emerging areas within the field. However, it is intended that the two volumes should, where possible, be retained together for reference purposes and our use of the term ‘book’ will generally refer to both volumes. In the first volume, Drug Transporters: Volume 1 Role and Importance in ADME and Drug Development, some of the basic concepts are introduced in the initial chapter, with subsequent chapters focusing on the key ADME organs (liver, gastrointestinal tract, kidney, blood–brain barrier and lung) and how the differential expression of a multitude of characterized drug transporters can impact the fate of both endogenous and exogenous compounds within the human body. The following two sections cover preclinical models (in silico, in vitro and in vivo), and modelling approaches used within the pharmaceutical industry and how these can be valuable tools in determining the importance and clinical impact of transporter mediated drug–drug interactions. The current regulatory guidance is also discussed in the context of transporters and their potential clinical impact. The second volume Drug Transporters: Volume 2: Recent Advances and Emerging Technologies, is dedicated to our final section on emerging transporter science, introducing some of the newer areas and technologies where research is ongoing but is not necessarily part of routine investigations. Topics range from factors that may impact transporter form and function (regulation of expression, enzyme–transporter interplay and pharmacogenomics) through to more practical approaches to improve our understanding of transporter–mediated interactions (using microfluidics, proteomics, in vivo imaging and bioinformatics/cheminformatics). Transporters in other organs and tissues of the body, not covered in Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development, are also briefly discussed. This section serves to illustrate not only how the transporter field is progressing in many different areas, but also how our knowledge is still incomplete, with much still to be done.

In completing our original aim, it was clear that a book such as this could only be achieved through collaboration—from the initial ideas and support of the Royal Society of Chemistry and the Drug Metabolism Discussion Group (DMDG), through to the cooperation and efforts of a total of 61 authors who are experts in their fields, drawn from industry, academia, commercial laboratories and regulatory authorities in Europe, the USA and Asia. The involvement and continued commitment to this book from all of our collaborators was outstanding, especially given their ongoing workloads, and we remain indebted to them. Mention should also be made of our steering team of scientists, for their invaluable input into formulating the overall book outline, and to our panel of external reviewers, whose input helped to ensure that the scientific content of the book was accurate and up to date.

Given the many months dedicated to this work by such an extensive network of expert scientists, we sincerely hope that this translates into a book that will be used by many people in the coming years as a valuable source of reference.

Glynis Nicholls

Kuresh Youdim