Ronald T. Borchardt – författare

Pharmaceutical scientists in industry and academia will appreciate this single reference for its detailed experimental procedures for conducting biopharmaceutical studies. This well-illustrated guide allows them to establish, validate, and implement commonly used in situ and in vitro model systems. Chapters provide ready access to these methodologies for studies of the intestinal, buccal, nasal and respiratory, vaginal, ocular, and dermal epithelium as well as the endothelial and elimination barriers.

In the late 1980s, it became painfully evident to the pharmaceutical industry that the old paradigm of drug discovery, which involved highly segmented drug - sign and development activities, would not produce an acceptable success rate in the future. Therefore, in the early 1990s a paradigm shift occurred in which drug design and development activities became more highly integrated. This new str- egy required medicinal chemists to design drug candidates with structural f- tures that optimized pharmacological (e. g. , high affinity and specificity for the target receptor), pharmaceutical (e. g. , solubility and chemical stability), bioph- maceutical (e. g. , cell membrane permeability), and metabolic/pharmacokinetic (e. g. , metabolic stability, clearance, and protein binding) properties. Successful implementation of this strategy requires a multidisciplinary team effort, incl- ing scientists from drug design (e. g. , medicinal chemists, cell biologists, en- mologists, pharmacologists) and drug development (e. g. , analytical chemists, pharmaceutical scientists, physiologists, and molecular biologists representing the disciplines of pharmaceutics, biopharmaceutics, and pharmacokinetics/drug metabolism). With this new, highly integrated approach to drug design now widely utilized by the pharmaceutical industry, the editors of this book have provided the sci- tific community with case histories to illustrate the nature of the interdisciplinary interactions necessary to successfully implement this new approach to drug d- covery. In the first chapter, Ralph Hirschmann provides a historical perspective of why this paradigm shift in drug discovery has occurred.

In the late 1980s, it became painfully evident to the pharmaceutical industry that the old paradigm of drug discovery, which involved highly segmented drug - sign and development activities, would not produce an acceptable success rate in the future. Therefore, in the early 1990s a paradigm shift occurred in which drug design and development activities became more highly integrated. This new str- egy required medicinal chemists to design drug candidates with structural f- tures that optimized pharmacological (e. g. , high affinity and specificity for the target receptor), pharmaceutical (e. g. , solubility and chemical stability), bioph- maceutical (e. g. , cell membrane permeability), and metabolic/pharmacokinetic (e. g. , metabolic stability, clearance, and protein binding) properties. Successful implementation of this strategy requires a multidisciplinary team effort, incl- ing scientists from drug design (e. g. , medicinal chemists, cell biologists, en- mologists, pharmacologists) and drug development (e. g. , analytical chemists, pharmaceutical scientists, physiologists, and molecular biologists representing the disciplines of pharmaceutics, biopharmaceutics, and pharmacokinetics/drug metabolism). With this new, highly integrated approach to drug design now widely utilized by the pharmaceutical industry, the editors of this book have provided the sci- tific community with case histories to illustrate the nature of the interdisciplinary interactions necessary to successfully implement this new approach to drug d- covery. In the first chapter, Ralph Hirschmann provides a historical perspective of why this paradigm shift in drug discovery has occurred.

Because the delivery of precise quantities of drugs to specific sites on an optimal schedule is one of the most complex problems in clinical pharmacology and therapeutics today, Borchardt, Repta and Stella have striven to organize in this text a wide-ranging review of the subject. Coverage of nearly all of the key physical, chemical, and biological aspects of targeted drug delivery is provided by an internationally prominent cadre of authors, and includes treatment of: pharmacodynamics; pharmocokinetic factors; molecular mechanisms; therapeutic variables; receptors and delivery; "in vivo" electrochemistry; chromatographic analysis; microparticulate carriers; biodegradable systems; macromolecular systems; monoclonal antibody carriers; prodrugs; scintigraphy; physicochemical variables; the GI, blood-brain and dermal barriers.

This book has been developed from its earlier and far less formal presentment as the proceedings of a symposium entitled The Biochemistry of S-Adenosylmethionine as a Basis for Drug Design that was held at the Solstrand Fjord Hotel in Bergen, Norway on June 30-July 4, 1985. The purpose of the symposium was to bring together scientists from various disciplines (biochemistry, pharmacology, virology, immunology, chemistry, medicine, and so on) to discuss the recent advances that have been made in our understanding of the biological roles of S­ adenosylmethionine (AdoMet) and to discuss the feasibility of utilizing AdoMet-dependent enzymes as targets for drug design. Thus the information provided herein will be of value not only to basic scientists involved in elucidating the role of AdoMet in biology, but also to medicinal chemists who are using this basic knowledge in the process of drug design. The volume should also be of interest to pharmacologists and clinicians involved in biological evaluation of potential therapeutic agents arising from the efforts of the biochemists and medicinal chemists. Each plenary speaker at the symposium was requested to submit a chapter reviewing recent contributions of their discipline to our base of knowledge about the biological role of AdoMet. Topics covered in this volume include protein and phospholipid methylations (Section A), nucleic acid methyl­ ations (Section B), the regulation of AdoMet, S-adenosylhomocysteine, and methylthioadenosine metabolism (Section C), clinical aspects of AdoMet (Section D), and the design, synthesis, and biological evaluation of trans­ methylation inhibitors (Section E).

This volume provides case histories illustrating the types of interdisciplinary interactions necessary to design drug candidates with optimal pharmacological, pharmaceutical, biopharmaceutical, and metabolic/pharmacokinetic properties. Key features include an incisive discussion of HIV protease inhibitors and 287 illustrations.

This book has been developed from its earlier and far less formal presentment as the proceedings of a symposium entitled The Biochemistry of S-Adenosylmethionine as a Basis for Drug Design that was held at the Solstrand Fjord Hotel in Bergen, Norway on June 30-July 4, 1985. The purpose of the symposium was to bring together scientists from various disciplines (biochemistry, pharmacology, virology, immunology, chemistry, medicine, and so on) to discuss the recent advances that have been made in our understanding of the biological roles of S­ adenosylmethionine (AdoMet) and to discuss the feasibility of utilizing AdoMet-dependent enzymes as targets for drug design. Thus the information provided herein will be of value not only to basic scientists involved in elucidating the role of AdoMet in biology, but also to medicinal chemists who are using this basic knowledge in the process of drug design. The volume should also be of interest to pharmacologists and clinicians involved in biological evaluation of potential therapeutic agents arising from the efforts of the biochemists and medicinal chemists. Each plenary speaker at the symposium was requested to submit a chapter reviewing recent contributions of their discipline to our base of knowledge about the biological role of AdoMet. Topics covered in this volume include protein and phospholipid methylations (Section A), nucleic acid methyl­ ations (Section B), the regulation of AdoMet, S-adenosylhomocysteine, and methylthioadenosine metabolism (Section C), clinical aspects of AdoMet (Section D), and the design, synthesis, and biological evaluation of trans­ methylation inhibitors (Section E).

This book is based on the proceedings of the symposium entitled "Di­ rected Drug Delivery: A Multidisciplinary Problem," which was held in Lawrence, Kansas on October 17-19, 1984. The purpose of the sym­ posium and this book is to focus on the multidisciplinary nature of drug delivery. Development of a successful drug delivery system re­ quires contributions from various scientific disciplines, including pharmaceutical chemistry, analytical chemistry, medicinal chemistry, biochemistry, pharmacology, toxicology, and clinical medicine. The contents of this volume illustrate the importance of the various disci­ plines in identifying the problems and approaches for the develop­ ment of a rational and effective drug delivery system. Thus the infor­ mation provided herein will be of value not only to the pharmaceutical chemists who are responsible for dosage form design, but also to the pharmacokineticists, pharmacologists, and clinicians involved in bio­ logical evaluation of drug delivery systems. The volume should also be of interest to the analytical chemists who must provide technology to quantitcltively evaluate drug delivery. Additionally, this work will also interest the biochemists and medicinal chemists involved in drug dis­ covery, since the drug delivery system often plays a major role in determining the success or failure of a new drug entity. Each speaker at the symposium was requested to contribute a chapter reviewing the contribution of their major discipline to the de­ velopment of a successful drug delivery system.

This book has been developed from its earlier and far less formal presentment as the proceedings of a symposium entitled The Biochemistry of S-Adenosylmethionine as a Basis for Drug Design that was held at the Solstrand Fjord Hotel in Bergen, Norway on June 30-July 4, 1985. The purpose of the symposium was to bring together scientists from various disciplines (biochemistry, pharmacology, virology, immunology, chemistry, medicine, and so on) to discuss the recent advances that have been made in our understanding of the biological roles of S­ adenosylmethionine (AdoMet) and to discuss the feasibility of utilizing AdoMet-dependent enzymes as targets for drug design. Thus the information provided herein will be of value not only to basic scientists involved in elucidating the role of AdoMet in biology, but also to medicinal chemists who are using this basic knowledge in the process of drug design. The volume should also be of interest to pharmacologists and clinicians involved in biological evaluation of potential therapeutic agents arising from the efforts of the biochemists and medicinal chemists. Each plenary speaker at the symposium was requested to submit a chapter reviewing recent contributions of their discipline to our base of knowledge about the biological role of AdoMet. Topics covered in this volume include protein and phospholipid methylations (Section A), nucleic acid methyl­ ations (Section B), the regulation of AdoMet, S-adenosylhomocysteine, and methylthioadenosine metabolism (Section C), clinical aspects of AdoMet (Section D), and the design, synthesis, and biological evaluation of trans­ methylation inhibitors (Section E).

This book is based on the proceedings of the symposium entitled "Di­ rected Drug Delivery: A Multidisciplinary Problem," which was held in Lawrence, Kansas on October 17-19, 1984. The purpose of the sym­ posium and this book is to focus on the multidisciplinary nature of drug delivery. Development of a successful drug delivery system re­ quires contributions from various scientific disciplines, including pharmaceutical chemistry, analytical chemistry, medicinal chemistry, biochemistry, pharmacology, toxicology, and clinical medicine. The contents of this volume illustrate the importance of the various disci­ plines in identifying the problems and approaches for the develop­ ment of a rational and effective drug delivery system. Thus the infor­ mation provided herein will be of value not only to the pharmaceutical chemists who are responsible for dosage form design, but also to the pharmacokineticists, pharmacologists, and clinicians involved in bio­ logical evaluation of drug delivery systems. The volume should also be of interest to the analytical chemists who must provide technology to quantitcltively evaluate drug delivery. Additionally, this work will also interest the biochemists and medicinal chemists involved in drug dis­ covery, since the drug delivery system often plays a major role in determining the success or failure of a new drug entity. Each speaker at the symposium was requested to contribute a chapter reviewing the contribution of their major discipline to the de­ velopment of a successful drug delivery system.

Pharmaceutical scientists in industry and academia will appreciate this single reference for its detailed experimental procedures for conducting biopharmaceutical studies. This well-illustrated guide allows them to establish, validate, and implement commonly used in situ and in vitro model systems. Chapters provide ready access to these methodologies for studies of the intestinal, buccal, nasal and respiratory, vaginal, ocular, and dermal epithelium as well as the endothelial and elimination barriers.