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Drug toxicokinetics
TiPS - November 1993 [Vol. 141
Safe and Sound Drug Toxicokinetics edited by Peter G. Welling and Felix de la Inglesia, Marcel Dekker, 1993. $250.00 (xviii + 408 pages) ISZV 0 8247 9019 7 This book could not be more timely since toxicokinetics is one of the subjects on the agenda for the Second International Conference on Harmonization of Drug Regulatory Requirements (ICH-2), which is to be held in Orlando in November this year. The preface introduces toxicokinetics as a rapidly emerging and evolving discipline in drug development, and sets out the aim of the book, to act as a manual for those involved in all aspects of safety testing. The book achieves this aim in that many of the chapters successfully introduce and illustrate how an understanding of the kinetic aspects of drugs can aid, or indeed explain, the results of animal toxicology studies. However, I suspect that it will be of more help to toxicologists than to professional kineticists, but it may act as a useful introduction for those new to, or on the periphery of, drug kinetics. Substantial coverage is given to the significance of toxicokinetics to the evaluation of drug safety. There is a danger in a multi-author book of this type that deals with a relatively new area that different contributors will use different definitions, but most of the authors work with the broad definition of toxicokinetics encompassing all aspects of drug kinetics at high doses (absorption, distribution, metabolism and excretion). Unfortunately, the ICH working party on toxicokinetics has recently, and probably after this book was published, restricted its definition to the rather narrower field of plasma drug level determination in toxicity studies. The most useful chapters included reviews on good laboratory practice, pharmacokinetics and several on study design, together with a range of examples. I particularly enjoyed the chapter dealing ;tiith the safety testing
419
of antischlerotic compounds. Regardless of the pharmacological action of the drugs, it was refreshing to see how the authors used real data to illustrate examples and pull the whole thing together. An otherwise excellent chapter on pharmacokinetics was spoilt by the (unwritten) suggestion that meaningful pharmacokinetic parameters could be generated from undifferentiated radioactivity data. This is a common misapprehension of many non-kineticists and, given the readership that will find this book most useful, this was an opportunity missed to help put matters straight. A couple of chapters did not come up to the standard of the others: the chapter on biochemical transformation to reactive metabolites seemed to add little, and the chapter on toxicity, kinetics and renal disease was largely a review of kidney toxicity and did not appear to correlate kinetics with toxicity to a significant degree. I felt that a number of authors had largely reproduced previously reviewed data without bothering to introduce more up-to-date data as some chapters contained a rather low proportion of references later than 1990. I was disappointed that the book did not mention the ICH process. Although creation of a book takes time, ICH has been
around for some years now and is of sufficient impact to be important to virtually all of the authors, so that they must have been aware of it. Similarly, future perspectives seemed to be the place to highlight the exciting challenges and potential for the future in such areas as molecular biology for enzyme characterization, developments to produce more sensitive assays and the possibilities in population kinetics to enable more to be derived from study animals. The final chapter, I felt, did not say anything new. Overall, the book does satisfy the aims in the preface of providing a textbook or reference guide. As 1 said previously, its primary audience will be toxicologists and the book will remind them of the factors that can influence their results. It will also be useful to others in the drug development process as an introduction to the primary reasons for studying drug metabolism and pharmacokinetics in animals. It is unlikely to become a ‘bible’ for professionals in the area, if for no other reason than the timing of its publication relative to ICH-2. Other than the definition of the term, ICH-2 will probably not result in any significant changes that will grossly outdate the book for some time to come. The significant changes will come from the science mentioned above. ALAN WARRANDER Safety
of Medicines Department. Zeneca
Phmtmceuticals. Mereside, Alderley Park, Maccfesfield, Cheshire, UK SKID 4TG.
iary Entry in the Diary section is free of charge and appropriate conferences and courses will be included when space is available. Entries for the Diary section should be addressed to the Editorial Secretary and sent at least six months before the event is scheduled to take place.
Safe and Sound Drug Toxicokinetics edited by Peter G. Welling and Felix de la Inglesia, Marcel Dekker, 1993. $250.00 (xviii + 408 pages) ISZV 0 8247 9019 7 This book could not be more timely since toxicokinetics is one of the subjects on the agenda for the Second International Conference on Harmonization of Drug Regulatory Requirements (ICH-2), which is to be held in Orlando in November this year. The preface introduces toxicokinetics as a rapidly emerging and evolving discipline in drug development, and sets out the aim of the book, to act as a manual for those involved in all aspects of safety testing. The book achieves this aim in that many of the chapters successfully introduce and illustrate how an understanding of the kinetic aspects of drugs can aid, or indeed explain, the results of animal toxicology studies. However, I suspect that it will be of more help to toxicologists than to professional kineticists, but it may act as a useful introduction for those new to, or on the periphery of, drug kinetics. Substantial coverage is given to the significance of toxicokinetics to the evaluation of drug safety. There is a danger in a multi-author book of this type that deals with a relatively new area that different contributors will use different definitions, but most of the authors work with the broad definition of toxicokinetics encompassing all aspects of drug kinetics at high doses (absorption, distribution, metabolism and excretion). Unfortunately, the ICH working party on toxicokinetics has recently, and probably after this book was published, restricted its definition to the rather narrower field of plasma drug level determination in toxicity studies. The most useful chapters included reviews on good laboratory practice, pharmacokinetics and several on study design, together with a range of examples. I particularly enjoyed the chapter dealing ;tiith the safety testing
419
of antischlerotic compounds. Regardless of the pharmacological action of the drugs, it was refreshing to see how the authors used real data to illustrate examples and pull the whole thing together. An otherwise excellent chapter on pharmacokinetics was spoilt by the (unwritten) suggestion that meaningful pharmacokinetic parameters could be generated from undifferentiated radioactivity data. This is a common misapprehension of many non-kineticists and, given the readership that will find this book most useful, this was an opportunity missed to help put matters straight. A couple of chapters did not come up to the standard of the others: the chapter on biochemical transformation to reactive metabolites seemed to add little, and the chapter on toxicity, kinetics and renal disease was largely a review of kidney toxicity and did not appear to correlate kinetics with toxicity to a significant degree. I felt that a number of authors had largely reproduced previously reviewed data without bothering to introduce more up-to-date data as some chapters contained a rather low proportion of references later than 1990. I was disappointed that the book did not mention the ICH process. Although creation of a book takes time, ICH has been
around for some years now and is of sufficient impact to be important to virtually all of the authors, so that they must have been aware of it. Similarly, future perspectives seemed to be the place to highlight the exciting challenges and potential for the future in such areas as molecular biology for enzyme characterization, developments to produce more sensitive assays and the possibilities in population kinetics to enable more to be derived from study animals. The final chapter, I felt, did not say anything new. Overall, the book does satisfy the aims in the preface of providing a textbook or reference guide. As 1 said previously, its primary audience will be toxicologists and the book will remind them of the factors that can influence their results. It will also be useful to others in the drug development process as an introduction to the primary reasons for studying drug metabolism and pharmacokinetics in animals. It is unlikely to become a ‘bible’ for professionals in the area, if for no other reason than the timing of its publication relative to ICH-2. Other than the definition of the term, ICH-2 will probably not result in any significant changes that will grossly outdate the book for some time to come. The significant changes will come from the science mentioned above. ALAN WARRANDER Safety
of Medicines Department. Zeneca
Phmtmceuticals. Mereside, Alderley Park, Maccfesfield, Cheshire, UK SKID 4TG.
iary Entry in the Diary section is free of charge and appropriate conferences and courses will be included when space is available. Entries for the Diary section should be addressed to the Editorial Secretary and sent at least six months before the event is scheduled to take place.