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Pharmacokinetics, a Modern View
the serious reader to become more involved in the subject. Given the superficial nature of the book I would not recommend it as a text for students or as a reference for investigators who have had training or experience in clinical pharmacokinetics. Moreover, due to the lack of information regarding the clinical implementation of pharmacokinetics, practicing physicians with an interest in pharmacokinetics should be referred to other, more complete, texts. The text may have some utility for individuals with no previous training or experience in pharmacokinetics who are looking for a very basic primer on the subject. Thaddeus H. Grasela, Jr. The Clinical Pharmacokinetics Laboratory Millard Fillmore Hospital Buffalo, NY 14209
The Substance Abuse Problems, vol. 2-New Issues for the 1980s. Edited by Sidney Cohen. The Haworth Press, New YorWLondon, 1985. 323 pp. 16 x 23.5 cm. ISBN 0-86656368-7 and 0-86-656369-5. Hardback: $34.95, Softback: $19.95. Following a preface, which provides an overview of drug abuse and a review of major developments of the past few decades, this book focuses on three of the major drugs of abuse today, cocaine, marijuana, and alcohol. A major section of the book is devoted to examining both the pharmacological effects and societal impact of each of the substances in a thorough, but concise, manner. A section entitled “Other Mind-Altering Substances” deals more briefly with several additional drugs, e.g. methaqualone, codeine, and paregoric. The chapter on caffeine is particularly informative. The remaining two sections of the book address a large number of issues relating to the influence of drugs on society. Included are such primary contemporary concerns as drugs in the workplace, the use of mind-altering drugs by athletes, and the relationship between drug use and AIDS. The one glaring omission in this book is the lack of mention of nicotine, which does not even appear as an index item. In view of the increased realization of the powerful addictive properties of nicotine, the enormous health effects of smoking, and heightened recent concern over the hazards of so-called smokeless tobacco, failure to include nicotine in this book is a puzzling deficiency. Another criticism is the lack of specific literature citations in the text, although there is a bibliography at the end of each chapter. In summary, Dr. Cohen’s book is a n informative and easily read source of information on substance abuse that should be very useful to professionals in the field and anyone wishing to learn more about this important topic. John L. Egle Department of Pharmacology and Toxicology Medical College of Virginia Virginia Commonwealth University Richmond, VA 23298-0001
Pharmacokinetics and Pharmacodynamicsof Psychoactive Drugs. Edited by Gene Barnett and C. Nora Chiang. Biomedical Publications, Foster City, CA 94404. 1985. xv + 505 pp. 15 x 23 cm. ISBN 0-93-189020-9. $37.50.
This book comprises 23 chapters by well-qualified researchers, and deals with pharmacokinetic and pharmacodynamic aspects of all common psychoactive drugs. Major attention is centered on A9-tetrahydrocannabinol, the active psychotomimetic constituent of marihuana. Other major studies include cocaine and phencyclidine. However, other opiates such as morphine, methadone, meperidine, and naltrexone are also considered, and amphetamines and diazepines are reviewed. The book suffers from one major flaw, which is not of a technical nature. This involves the length of time that transpired from the time these papers were first presented a t a NIDA sponsored conference early in 1983, until the appearance of the book late in 1985. Much of the work on the pharmacokinetics and metabolism of A’-THC has already appeared elsewhere in books containing the proceedings of two major symposia on cannabinoids. Recently, moreover, extensive reviews have been published. The same applies for phencyclidine. Nevertheless, the idea of putting together in one volume reviews of the pharmacokinetics and pharmacodynamics of the various psychoactive drugs was an excellent idea. Consequently this book will be a valuable reference source, including, as it does in one convenient locus, a number of excellent studies. The papers dealing with cocaine, particularly the free base, are timely now because of the current prevalence of cocaine abuse in this form. Although the pharmacokinetics and metabolism of some of these drugs, particularly AS-THC, are well established, the pharmacodynamic principles or the combination of pharmacokinetics and pharmacodynamics are less well understood, and the inclusion of articles on this subject is useful. Three analytical papers are presented a t the end of this book. Because of the rapid developments in the area of HPLC, the article dealing with the use of these techniques with psychoactive drugs is now probably unfortunately dated, but it still has useful information. The paper dealing with the mass spectrometry of cannabinoids is classical in its scope and should be required reading for both experienced and recent practitioners who work in this area. There is a brief index, probably too brief, but still useful enough so that one can readily find the papers which deal with a particular drug of interest. In conclusion, then, “Pharmacokinetics and Pharmacodynamics of Psychoactive Drugs” will be a useful reference volume for some years to come for workers in this field. It is particularly noteworthy in that one can find excellent reviews on virtually all drugs of abuse in one volume. It should be in the collections of all workers in the field as well as in technical reference libraries. Monroe E. Wall Research Triangle Institute Research Triangle Park, NC 27709
Pharmacokinetics, A Modern View. Edited by L. 2. Benet, G.Levy, and 8. L. Ferraiolo. Plenum Press, New York, 1984. xvi + 531 pp. 17 x 26 cm. ISBN 0-306-4180-. $65.00. In this volume, under the title “Pharmacokinetics, A Modern View,” is published the proceedings of the Sidney Riegelman Memorial Symposium, held from April 22-24, 1982, at the University of California, San Francisco, CA. This symposium was dedicated to one of the most eminent scientists in the field of pharmaceutical sciences and one of the founders of, and leaders in, pharmacokinetics and bioJournal of Pharmaceutical Sciences / 825 Vol. 75, No. 8, August 1986
pharmaceutics, who died tragically in an accident on April 4, 1981. His impact is demonstrated by the fact that twenty-two graduate students received their Ph.D.’s under Prof. Riegelman’s direction and a similar number of postdoctoral scholars from all over the world have worked in his laboratory. Thirty-two of these Riegelman-trained scientists were authors of chapters of this book. The first six chapters are dedicated to the life of Prof. Riegelman and are presented by close friends and colleagues. They give a good impression of his training, his early pharmaceutical career, his role as educator and scientist, and his contributions to public pharmacy. These pages are of historical value .because they illustrate so well his broad interest in the pharmaceutical sciences, the fact that he was a pharmacist “pur sang”, as well as his warm personality and the fact that he was a friend and confidant of so many students and colleagues. The actual proceedings of the symposium form the remainder of the book. It contains the text of 22 lectures given by leading scientists in the field of biopharmaceutics and pharmacokinetics. The book is divided into the following chapters: Biopharmaceutics-Drug Delivery; Pharmacokinetics-Concepts, Theory and Application; Pharmacokinetics and Drug Metabolism; Pharmacokinetics-Drug Dosing and Drug Effects and Pharmacokinetics and Biopharmaceutics of Chemotherapeutic and Immunosuppressive Agents. As the contents of these chapters show, the organizers of the meeting and the editors of this book have been successful in demonstrating Prof. Riegelman’s wide interest in the newest developments of concepts such as nonlinear pharmacokinetics, physiologically based models, presystemic biotransformation, effects of age and disease on drug disposition, relationship between plasma protein binding and drug distribution and elimination, kinetics of pharmacodynamic effects, and population pharmacokinetics. This part of the book is a unique collection of fine papers by the most prominent scientists in this field. In the second part of the proceedings, the younger generation-almost all of them former students or visiting scientists from abroad-reports in 31 4-page abstracts about their recent research, a large proportion of which was performed under the guidance of Prof. Riegelman. An Appendix lists a scientific bibliography of all 174 papers that were written or co-authored by Prof. Riegelman. This illustrates again the multifarious interests of this brilliant pharmaceutical scientist. The fact that about 25 of these papers were published after his death demonstrates how active he was when he left us too early. The book ends with an index which makes it highly accessible. By virtue of its subjectdedication to Prof. Riegelman-and by the high standard of its contents this book rises far above the level of the normal proceedings of a scientific meeting. It is a must for everyone who is interested in the life of a great scientist, the history of the pharmaceutical sciences,and the latest concepts in pharmacokinetics. Dr. Jan H. G. Jonkman State University of Groningen The Netherlands
Nonsteroldal Antllnflammatory Drugs, vol. 5, Chemistry and Pharmacology of Drugs. Edited by Joseph G. Lombardino; series editor is Daniel Lednicer. John Wiley and Sons, Inc., New York, NY 10158.1985.447 pp. 16 x 23.5 cm. ISBN: 0-471-89803-1. “Nonsteroidal Antiinflammatory Drugs”, edited by Joseph 826 / Journal of Pharmaceutical Sciences Vol. 75, No. 8, August 1986
G.Lombardino, is Volume 5 in a series entitled Chemistry and Pharmacology of Drugs. The aims of this text are noble since it is hoped that the book will be a valuable reference tool for both pharmacologists and medicinal chemists who wish to develop superior antiinflammatory agents. To create a wide appeal, the book is divided into four chapters, “Normal Articular Cartiliage and the Alterations in Osteoarthritis”, “Inflammation-Mechanisms and Mediators”, “Laboratory Models for Testing Nonsteroidal Antiinflammatory Drugs”, and “Medicinal Chemistry of Acidic Nonsteroidal Antiinflammatory Drugs.” The first chapter offers an extensive review on the macroand microscopic structures of articular cartilage. It describes in detail a t the molecular level the structure of collagen and proteoglycans. Alterations in structure of the cartilage and chondrocyte behavior in osteroarthritis are discussed. This chapter would be overwhelming to a reader who wishes more knowledge of the pharmacology of nonsteroidal antiinflammatory drugs, and I wonder whether all of this structural information is necessary. In the subsequent chapter on mediators of inflammation, the book remains unbalanced in its approach. Three to four pages are devoted to the prostaglandins and one to the leukotrienes. Since the accepted mechanism of action of nonsteroidal antiinflammatory drugs is inhibition of prostaglandin synthetase, it is sad to see that this section is limited. Indeed this chapter seems to catalogue the essential mediators of inflammation without giving a n in-depth discussion. This chapter appears to be particularly unbalanced when the reader has just ploughed through 54 pages on the structure of articular cartiliage. The third chapter describes in exacting detail in vivo tests for nonsteroidal antiinflammatory drug potency and will be especially helpful to any research group wishing to establish these assays in their laboratory. However, as too much space is given to some of the finer points of the various methods, this chapter could be condensed from its 130 pages of text. Dr. Lombardino has made a commendable effort in the final chapter of the book to discuss the medicinal chemistry of some 67 nonsteroidal antiinflammatory drugs. An omission appears to be the para-aminophenol derivatives represented by acetaminophen and phenacetin. Presumably this omission is due to the fact that these agents are effective analgesics but have no antiinflammatory activity. In dealing with each agent, Dr. Lombardino discusses the development of the drug and its synthesis, describes some salient features of the QSAR performed, and gives some data on the disposition of the drug. A chapter which this book lacks is one which deals in a single place with the mechanism of action of nonsteroidal antiinflammatory drugs, their pharmacology, and therapeutics. This reviewer was constantly searching for an account of this material. It is true that since the acceptance of Vane’s hypothesis, which states that these drugs inhibit prostaglandin synthetase, a plethora of review articles have been written on this subject. However, any text entitled “Nonsteroidal Antiinflammatory Drugs” should contain a thorough review of the work in this area. Moreover, a scholarly discussion concerning Vane’s hypothesis would reveal the various inconsistencies that exist. For example, why is it that the nonacetylated salicylates (e.g. sodium salicylate) are as analgesic, antipyretic, and antiinflammatory as aspirin, but do not inhibit prostaglandin biosynthesis? Why is it that acetaminophen is as analgesic as aspirin but displays no effect on inflammation? Discussion of these topics might lead the reader to consider some alternative modes of action for these drugs. Other modes of action have been described in the literature. These should be considerd if the text is to fulfill its objective in helping researchers develop superior antiinflam-
The Substance Abuse Problems, vol. 2-New Issues for the 1980s. Edited by Sidney Cohen. The Haworth Press, New YorWLondon, 1985. 323 pp. 16 x 23.5 cm. ISBN 0-86656368-7 and 0-86-656369-5. Hardback: $34.95, Softback: $19.95. Following a preface, which provides an overview of drug abuse and a review of major developments of the past few decades, this book focuses on three of the major drugs of abuse today, cocaine, marijuana, and alcohol. A major section of the book is devoted to examining both the pharmacological effects and societal impact of each of the substances in a thorough, but concise, manner. A section entitled “Other Mind-Altering Substances” deals more briefly with several additional drugs, e.g. methaqualone, codeine, and paregoric. The chapter on caffeine is particularly informative. The remaining two sections of the book address a large number of issues relating to the influence of drugs on society. Included are such primary contemporary concerns as drugs in the workplace, the use of mind-altering drugs by athletes, and the relationship between drug use and AIDS. The one glaring omission in this book is the lack of mention of nicotine, which does not even appear as an index item. In view of the increased realization of the powerful addictive properties of nicotine, the enormous health effects of smoking, and heightened recent concern over the hazards of so-called smokeless tobacco, failure to include nicotine in this book is a puzzling deficiency. Another criticism is the lack of specific literature citations in the text, although there is a bibliography at the end of each chapter. In summary, Dr. Cohen’s book is a n informative and easily read source of information on substance abuse that should be very useful to professionals in the field and anyone wishing to learn more about this important topic. John L. Egle Department of Pharmacology and Toxicology Medical College of Virginia Virginia Commonwealth University Richmond, VA 23298-0001
Pharmacokinetics and Pharmacodynamicsof Psychoactive Drugs. Edited by Gene Barnett and C. Nora Chiang. Biomedical Publications, Foster City, CA 94404. 1985. xv + 505 pp. 15 x 23 cm. ISBN 0-93-189020-9. $37.50.
This book comprises 23 chapters by well-qualified researchers, and deals with pharmacokinetic and pharmacodynamic aspects of all common psychoactive drugs. Major attention is centered on A9-tetrahydrocannabinol, the active psychotomimetic constituent of marihuana. Other major studies include cocaine and phencyclidine. However, other opiates such as morphine, methadone, meperidine, and naltrexone are also considered, and amphetamines and diazepines are reviewed. The book suffers from one major flaw, which is not of a technical nature. This involves the length of time that transpired from the time these papers were first presented a t a NIDA sponsored conference early in 1983, until the appearance of the book late in 1985. Much of the work on the pharmacokinetics and metabolism of A’-THC has already appeared elsewhere in books containing the proceedings of two major symposia on cannabinoids. Recently, moreover, extensive reviews have been published. The same applies for phencyclidine. Nevertheless, the idea of putting together in one volume reviews of the pharmacokinetics and pharmacodynamics of the various psychoactive drugs was an excellent idea. Consequently this book will be a valuable reference source, including, as it does in one convenient locus, a number of excellent studies. The papers dealing with cocaine, particularly the free base, are timely now because of the current prevalence of cocaine abuse in this form. Although the pharmacokinetics and metabolism of some of these drugs, particularly AS-THC, are well established, the pharmacodynamic principles or the combination of pharmacokinetics and pharmacodynamics are less well understood, and the inclusion of articles on this subject is useful. Three analytical papers are presented a t the end of this book. Because of the rapid developments in the area of HPLC, the article dealing with the use of these techniques with psychoactive drugs is now probably unfortunately dated, but it still has useful information. The paper dealing with the mass spectrometry of cannabinoids is classical in its scope and should be required reading for both experienced and recent practitioners who work in this area. There is a brief index, probably too brief, but still useful enough so that one can readily find the papers which deal with a particular drug of interest. In conclusion, then, “Pharmacokinetics and Pharmacodynamics of Psychoactive Drugs” will be a useful reference volume for some years to come for workers in this field. It is particularly noteworthy in that one can find excellent reviews on virtually all drugs of abuse in one volume. It should be in the collections of all workers in the field as well as in technical reference libraries. Monroe E. Wall Research Triangle Institute Research Triangle Park, NC 27709
Pharmacokinetics, A Modern View. Edited by L. 2. Benet, G.Levy, and 8. L. Ferraiolo. Plenum Press, New York, 1984. xvi + 531 pp. 17 x 26 cm. ISBN 0-306-4180-. $65.00. In this volume, under the title “Pharmacokinetics, A Modern View,” is published the proceedings of the Sidney Riegelman Memorial Symposium, held from April 22-24, 1982, at the University of California, San Francisco, CA. This symposium was dedicated to one of the most eminent scientists in the field of pharmaceutical sciences and one of the founders of, and leaders in, pharmacokinetics and bioJournal of Pharmaceutical Sciences / 825 Vol. 75, No. 8, August 1986
pharmaceutics, who died tragically in an accident on April 4, 1981. His impact is demonstrated by the fact that twenty-two graduate students received their Ph.D.’s under Prof. Riegelman’s direction and a similar number of postdoctoral scholars from all over the world have worked in his laboratory. Thirty-two of these Riegelman-trained scientists were authors of chapters of this book. The first six chapters are dedicated to the life of Prof. Riegelman and are presented by close friends and colleagues. They give a good impression of his training, his early pharmaceutical career, his role as educator and scientist, and his contributions to public pharmacy. These pages are of historical value .because they illustrate so well his broad interest in the pharmaceutical sciences, the fact that he was a pharmacist “pur sang”, as well as his warm personality and the fact that he was a friend and confidant of so many students and colleagues. The actual proceedings of the symposium form the remainder of the book. It contains the text of 22 lectures given by leading scientists in the field of biopharmaceutics and pharmacokinetics. The book is divided into the following chapters: Biopharmaceutics-Drug Delivery; Pharmacokinetics-Concepts, Theory and Application; Pharmacokinetics and Drug Metabolism; Pharmacokinetics-Drug Dosing and Drug Effects and Pharmacokinetics and Biopharmaceutics of Chemotherapeutic and Immunosuppressive Agents. As the contents of these chapters show, the organizers of the meeting and the editors of this book have been successful in demonstrating Prof. Riegelman’s wide interest in the newest developments of concepts such as nonlinear pharmacokinetics, physiologically based models, presystemic biotransformation, effects of age and disease on drug disposition, relationship between plasma protein binding and drug distribution and elimination, kinetics of pharmacodynamic effects, and population pharmacokinetics. This part of the book is a unique collection of fine papers by the most prominent scientists in this field. In the second part of the proceedings, the younger generation-almost all of them former students or visiting scientists from abroad-reports in 31 4-page abstracts about their recent research, a large proportion of which was performed under the guidance of Prof. Riegelman. An Appendix lists a scientific bibliography of all 174 papers that were written or co-authored by Prof. Riegelman. This illustrates again the multifarious interests of this brilliant pharmaceutical scientist. The fact that about 25 of these papers were published after his death demonstrates how active he was when he left us too early. The book ends with an index which makes it highly accessible. By virtue of its subjectdedication to Prof. Riegelman-and by the high standard of its contents this book rises far above the level of the normal proceedings of a scientific meeting. It is a must for everyone who is interested in the life of a great scientist, the history of the pharmaceutical sciences,and the latest concepts in pharmacokinetics. Dr. Jan H. G. Jonkman State University of Groningen The Netherlands
Nonsteroldal Antllnflammatory Drugs, vol. 5, Chemistry and Pharmacology of Drugs. Edited by Joseph G. Lombardino; series editor is Daniel Lednicer. John Wiley and Sons, Inc., New York, NY 10158.1985.447 pp. 16 x 23.5 cm. ISBN: 0-471-89803-1. “Nonsteroidal Antiinflammatory Drugs”, edited by Joseph 826 / Journal of Pharmaceutical Sciences Vol. 75, No. 8, August 1986
G.Lombardino, is Volume 5 in a series entitled Chemistry and Pharmacology of Drugs. The aims of this text are noble since it is hoped that the book will be a valuable reference tool for both pharmacologists and medicinal chemists who wish to develop superior antiinflammatory agents. To create a wide appeal, the book is divided into four chapters, “Normal Articular Cartiliage and the Alterations in Osteoarthritis”, “Inflammation-Mechanisms and Mediators”, “Laboratory Models for Testing Nonsteroidal Antiinflammatory Drugs”, and “Medicinal Chemistry of Acidic Nonsteroidal Antiinflammatory Drugs.” The first chapter offers an extensive review on the macroand microscopic structures of articular cartilage. It describes in detail a t the molecular level the structure of collagen and proteoglycans. Alterations in structure of the cartilage and chondrocyte behavior in osteroarthritis are discussed. This chapter would be overwhelming to a reader who wishes more knowledge of the pharmacology of nonsteroidal antiinflammatory drugs, and I wonder whether all of this structural information is necessary. In the subsequent chapter on mediators of inflammation, the book remains unbalanced in its approach. Three to four pages are devoted to the prostaglandins and one to the leukotrienes. Since the accepted mechanism of action of nonsteroidal antiinflammatory drugs is inhibition of prostaglandin synthetase, it is sad to see that this section is limited. Indeed this chapter seems to catalogue the essential mediators of inflammation without giving a n in-depth discussion. This chapter appears to be particularly unbalanced when the reader has just ploughed through 54 pages on the structure of articular cartiliage. The third chapter describes in exacting detail in vivo tests for nonsteroidal antiinflammatory drug potency and will be especially helpful to any research group wishing to establish these assays in their laboratory. However, as too much space is given to some of the finer points of the various methods, this chapter could be condensed from its 130 pages of text. Dr. Lombardino has made a commendable effort in the final chapter of the book to discuss the medicinal chemistry of some 67 nonsteroidal antiinflammatory drugs. An omission appears to be the para-aminophenol derivatives represented by acetaminophen and phenacetin. Presumably this omission is due to the fact that these agents are effective analgesics but have no antiinflammatory activity. In dealing with each agent, Dr. Lombardino discusses the development of the drug and its synthesis, describes some salient features of the QSAR performed, and gives some data on the disposition of the drug. A chapter which this book lacks is one which deals in a single place with the mechanism of action of nonsteroidal antiinflammatory drugs, their pharmacology, and therapeutics. This reviewer was constantly searching for an account of this material. It is true that since the acceptance of Vane’s hypothesis, which states that these drugs inhibit prostaglandin synthetase, a plethora of review articles have been written on this subject. However, any text entitled “Nonsteroidal Antiinflammatory Drugs” should contain a thorough review of the work in this area. Moreover, a scholarly discussion concerning Vane’s hypothesis would reveal the various inconsistencies that exist. For example, why is it that the nonacetylated salicylates (e.g. sodium salicylate) are as analgesic, antipyretic, and antiinflammatory as aspirin, but do not inhibit prostaglandin biosynthesis? Why is it that acetaminophen is as analgesic as aspirin but displays no effect on inflammation? Discussion of these topics might lead the reader to consider some alternative modes of action for these drugs. Other modes of action have been described in the literature. These should be considerd if the text is to fulfill its objective in helping researchers develop superior antiinflam-