The Biochemistry of Drug Metabolism, 2 Vols.
Principles, Redox Reactions, Hydrolyses; Conjugations, Consequences of Metabolism, Influencing Factors
(Sprache: Englisch)
Offering a conceptual and factual presentation of the metabolism of drugs and other xenobiotics, these two volumes distinctly focus on the biochemistry, with an emphasis on xenobiotic-metabolizing enzymes, their reactions and regulations.
The first volume is divided into three parts.
The first volume is divided into three parts.
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Offering a conceptual and factual presentation of the metabolism of drugs and other xenobiotics, these two volumes distinctly focus on the biochemistry, with an emphasis on xenobiotic-metabolizing enzymes, their reactions and regulations.
The first volume is divided into three parts.
The first volume is divided into three parts.
Klappentext zu „The Biochemistry of Drug Metabolism, 2 Vols. “
Offering a conceptual and factual presentation of the metabolism of drugs and other xenobiotics, these two volumes distinctly focus on the biochemistry, with an emphasis on xenobiotic-metabolizing enzymes, their reactions and regulations.The first volume is divided into three parts. Part One begins by introducing xenobiotics in the broad context of physiological metabolism, and continues with an overview of the processes of drug disposition and metabolism. It then goes on to summarize the macroscopic and microscopic locations of drug metabolism in animals and humans. This is followed by an introduction to the all-important issue of the consequences of drug and xenobiotic metabolism, providing an initial overview of pharmacokinetic, pharmacological and toxicological consequences. The last chapter examines drug metabolism in the context of drug research, with a focus on medicinal chemistry.The second part is a major component of the book, corresponding to the role of oxidoreductases as major agents of metabolism. Cytochromes P450 receive particular attention, namely their multiplicity, structure, catalytic mechanisms, and the various reactions they catalyze, while other oxidoreductases are also presented, such as flavin monooxygenases, monoamine oxidases and other amine oxidases, aldehyde oxidase and xanthine dehydrogenase, peroxidases, and dehydrogenases-reductases. Each drug-metabolizing enzyme or enzyme family begins with an Enzyme Identity Card summarizing its nomenclature and biochemical essentials.Part Three begins with a survey of the classification, properties and catalytic mechanism of the innumerable hydrolases known or suspected to play a role in xenobiotic metabolism. The focus then shifts to a systematic presentation of the various substrates classes, namely carboxylic esters, amides and peptides, lactams and lactones, esters of inorganic acids, alkene and arene epoxides, and some miscellaneous hydrolyzable moieties.Volume Two contains the last four parts
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of this work. Part 4 is devoted to the huge field of conjugation reactions, with much information being given on transferases. As in the two preceding parts, each drug-metabolizing enzyme or enzyme family begins with an Enzyme Identity Card summarizing its nomenclature and biochemical essentials. The reactions examined here include methylation, sulfation, glucuronidation, acetylation, conjugation with glutathione, while there is also a rigorous presentation of the pivotal role of xenobiotic-coenzyme A conjugates as a crossroads to various metabolic reactions.The next part examines the consequences of drug and xenobiotic metabolism in a pharmacological and toxicological perspective, with due attention paid to full activation, as is found with prodrugs, and to the worrying case of xenobiotic toxification. Parts 6 and 7 cover the inter-individual and intra-individual factors that influence drug metabolism, starting with an introduction to evolutionary events leading to species differences in the metabolism of xenobiotics and to polymorphisms within a particular species. Focusing on humans, the most relevant polymorphic drug-metabolizing enzymes are discussed, concentrating on ethnic differences and on the consequences for the pharmacokinetic behavior of affected drugs, while also introducing sex-dependent metabolic reactions. The final part introduces the mechanisms leading to increases or decreases in enzyme activities as the concept of enzyme induction via nuclear receptors and the different mechanisms of enzyme inhibition are explained. With these basics in mind, various influencing factors are discussed, including physiological and pathological conditions, as well as drugs, nutrients and environmental agents with a special focus on drug-drug interactions.With a foreword by Prof Leslie Z. Benet, the renowned biopharmaceutical scientist.
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Anhand von Theorien und Fakten wird in diesen zwei Bnden auf anschauliche Weise die biochemische Seite des Metabolismus von Wirkstoffen und anderen Fremdstoffen beleuchtet. Der Schwerpunkt liegt dabei auf den Fremdstoff-metabolisierenden Enzymen, ihren Reaktionen und Regulationen.
Im ersten Band schpfen die Autoren aus ihrer umfangreichen Erfahrung als Forscher und Hochschullehrer und bieten eine lebendige, beraus informative und vor allem lehrreiche Darstellung der drei Hauptaspekte des Arzneimittel- und Fremdstoffmetabolismus. Im ersten der drei Teile des Bands werden allgemeine Grundlagen erlutert und die schnelle Entwicklung auf diesem Gebiet betrachtet. Es wird eine erste bersicht ber die pharmakokinetischen, pharmakologischen und toxikologischen Auswirkungen gegeben. Der zweite Teil behandelt metabolische Reaktionen der Oxidation und Reduktion, wobei Cytochrome P450, ihre katalytischen Mechanismen und die verschiedenen Reaktionstypen, die sie katalysieren, besonders vertieft werden. Der dritte Teil widmet sich den unzhligen Hydrolasen, bei denen eine Beteiligung am Fremdstoffmetabolismus angenommen wird, und den vielen verschiedenen Substraten der Enzyme, die hydrolysiert werden.
Der zweite Band beschliet die allgemeine Beschreibung von Arzneimittel-metabolisierenden Enzymen und ihren katalysierten Reaktionen des ersten Bands. Nachdem im Teil 4 Konjugationsreaktionen und ihre jeweiligen katalysierenden Enzyme beschrieben wurden, behandelt Teil 5 die pharmakologischen und toxikologischen Auswirkungen des Arzneimittel- und Fremdstoffmetabolismus, die durch berzeugende Beispiele belegt werden. Die letzten zwei Teile untersuchen die inter- und intraindividuellen Faktoren, die die Expression und Aktivitt der Arzneimittel-metabolisierenden Enzyme beeinflussen, einschlielich genetischer Faktoren, wie die Unterschiede zwischen den tierischen Spezies und die Polymorphismen von menschlichen Arzneimittel-metabolisierenden Enzymen. Abschlieend werden genetisch unabhngige Einflussfaktoren beleuchtet, die sich whrend der Lebenszeit verndern knnen, im Mittelpunkt stehen dabei Arzneimittelwechselwirkungen.
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Offering a conceptual and factual presentation of the metabolism of drugs and other xenobiotics, these two volumes distinctly focus on the biochemistry, with an emphasis on xenobiotic-metabolizing enzymes, their reactions and regulations.
The first volume is divided into three parts. Part One begins by introducing xenobiotics in the broad context of physiological metabolism, and continues with an overview of the processes of drug disposition and metabolism. It then goes on to summarize the macroscopic and microscopic locations of drug metabolism in animals and humans. This is followed by an introduction to the all-important issue of the consequences of drug and xenobiotic metabolism, providing an initial overview of pharmacokinetic, pharmacological and toxicological consequences. The last chapter examines drug metabolism in the context of drug research, with a focus on medicinal chemistry.
The second part is a major component of the book, corresponding to the role of oxidoreductases as major agents of metabolism. Cytochromes P450 receive particular attention, namely their multiplicity, structure, catalytic mechanisms, and the various reactions they catalyze, while other oxidoreductases are also presented, such as flavin monooxygenases, monoamine oxidases and other amine oxidases, aldehyde oxidase and xanthine dehydrogenase, peroxidases, and dehydrogenases-reductases. Each drug-metabolizing enzyme or enzyme family begins with an Enzyme Identity Card summarizing its nomenclature and biochemical essentials.
Part Three begins with a survey of the classification, properties and catalytic mechanism of the innumerable hydrolases known or suspected to play a role in xenobiotic metabolism. The focus then shifts to a systematic presentation of the various substrates classes, namely carboxylic esters, amides and peptides, lactams and lactones, esters of inorganic acids, alkene and arene epoxides, and some miscellaneous hydrolyzable moieties.
Volume Two contains the last four parts of this work. Part 4 is devoted to the huge field of conjugation reactions, with much information being given on transferases. As in the two preceding parts, each drug-metabolizing enzyme or enzyme family begins with an Enzyme Identity Card summarizing its nomenclature and biochemical essentials. The reactions examined here include methylation, sulfation, glucuronidation, acetylation, conjugation with glutathione, while there is also a rigorous presentation of the pivotal role of xenobiotic-coenzyme A conjugates as a crossroads to various metabolic reactions.
The next part examines the consequences of drug and xenobiotic metabolism in a pharmacological and toxicological perspective, with due attention paid to full activation, as is found with prodrugs, and to the worrying case of xenobiotic toxification.
Parts 6 and 7 cover the inter-individual and intra-individual factors that influence drug metabolism, starting with an introduction to evolutionary events leading to species differences in the metabolism of xenobiotics and to polymorphisms within a particular species. Focusing on humans, the most relevant polymorphic drug-metabolizing enzymes are discussed, concentrating on ethnic differences and on the consequences for the pharmacokinetic behavior of affected drugs, while also introducing sex-dependent metabolic reactions.
The final part introduces the mechanisms leading to increases or decreases in enzyme activities as the concept of enzyme induction via nuclear receptors and the different mechanisms of enzyme inhibition are explained. With these basics in mind, various influencing factors are discussed, including physiological and pathological conditions, as well as drugs, nutrients and environmental agents with a special focus on drug-drug interactions.
With a foreword by Prof Leslie Z. Benet, the world's best and best-known biopharmaceutical scientist.
Im ersten Band schpfen die Autoren aus ihrer umfangreichen Erfahrung als Forscher und Hochschullehrer und bieten eine lebendige, beraus informative und vor allem lehrreiche Darstellung der drei Hauptaspekte des Arzneimittel- und Fremdstoffmetabolismus. Im ersten der drei Teile des Bands werden allgemeine Grundlagen erlutert und die schnelle Entwicklung auf diesem Gebiet betrachtet. Es wird eine erste bersicht ber die pharmakokinetischen, pharmakologischen und toxikologischen Auswirkungen gegeben. Der zweite Teil behandelt metabolische Reaktionen der Oxidation und Reduktion, wobei Cytochrome P450, ihre katalytischen Mechanismen und die verschiedenen Reaktionstypen, die sie katalysieren, besonders vertieft werden. Der dritte Teil widmet sich den unzhligen Hydrolasen, bei denen eine Beteiligung am Fremdstoffmetabolismus angenommen wird, und den vielen verschiedenen Substraten der Enzyme, die hydrolysiert werden.
Der zweite Band beschliet die allgemeine Beschreibung von Arzneimittel-metabolisierenden Enzymen und ihren katalysierten Reaktionen des ersten Bands. Nachdem im Teil 4 Konjugationsreaktionen und ihre jeweiligen katalysierenden Enzyme beschrieben wurden, behandelt Teil 5 die pharmakologischen und toxikologischen Auswirkungen des Arzneimittel- und Fremdstoffmetabolismus, die durch berzeugende Beispiele belegt werden. Die letzten zwei Teile untersuchen die inter- und intraindividuellen Faktoren, die die Expression und Aktivitt der Arzneimittel-metabolisierenden Enzyme beeinflussen, einschlielich genetischer Faktoren, wie die Unterschiede zwischen den tierischen Spezies und die Polymorphismen von menschlichen Arzneimittel-metabolisierenden Enzymen. Abschlieend werden genetisch unabhngige Einflussfaktoren beleuchtet, die sich whrend der Lebenszeit verndern knnen, im Mittelpunkt stehen dabei Arzneimittelwechselwirkungen.
----------------------------------------
Offering a conceptual and factual presentation of the metabolism of drugs and other xenobiotics, these two volumes distinctly focus on the biochemistry, with an emphasis on xenobiotic-metabolizing enzymes, their reactions and regulations.
The first volume is divided into three parts. Part One begins by introducing xenobiotics in the broad context of physiological metabolism, and continues with an overview of the processes of drug disposition and metabolism. It then goes on to summarize the macroscopic and microscopic locations of drug metabolism in animals and humans. This is followed by an introduction to the all-important issue of the consequences of drug and xenobiotic metabolism, providing an initial overview of pharmacokinetic, pharmacological and toxicological consequences. The last chapter examines drug metabolism in the context of drug research, with a focus on medicinal chemistry.
The second part is a major component of the book, corresponding to the role of oxidoreductases as major agents of metabolism. Cytochromes P450 receive particular attention, namely their multiplicity, structure, catalytic mechanisms, and the various reactions they catalyze, while other oxidoreductases are also presented, such as flavin monooxygenases, monoamine oxidases and other amine oxidases, aldehyde oxidase and xanthine dehydrogenase, peroxidases, and dehydrogenases-reductases. Each drug-metabolizing enzyme or enzyme family begins with an Enzyme Identity Card summarizing its nomenclature and biochemical essentials.
Part Three begins with a survey of the classification, properties and catalytic mechanism of the innumerable hydrolases known or suspected to play a role in xenobiotic metabolism. The focus then shifts to a systematic presentation of the various substrates classes, namely carboxylic esters, amides and peptides, lactams and lactones, esters of inorganic acids, alkene and arene epoxides, and some miscellaneous hydrolyzable moieties.
Volume Two contains the last four parts of this work. Part 4 is devoted to the huge field of conjugation reactions, with much information being given on transferases. As in the two preceding parts, each drug-metabolizing enzyme or enzyme family begins with an Enzyme Identity Card summarizing its nomenclature and biochemical essentials. The reactions examined here include methylation, sulfation, glucuronidation, acetylation, conjugation with glutathione, while there is also a rigorous presentation of the pivotal role of xenobiotic-coenzyme A conjugates as a crossroads to various metabolic reactions.
The next part examines the consequences of drug and xenobiotic metabolism in a pharmacological and toxicological perspective, with due attention paid to full activation, as is found with prodrugs, and to the worrying case of xenobiotic toxification.
Parts 6 and 7 cover the inter-individual and intra-individual factors that influence drug metabolism, starting with an introduction to evolutionary events leading to species differences in the metabolism of xenobiotics and to polymorphisms within a particular species. Focusing on humans, the most relevant polymorphic drug-metabolizing enzymes are discussed, concentrating on ethnic differences and on the consequences for the pharmacokinetic behavior of affected drugs, while also introducing sex-dependent metabolic reactions.
The final part introduces the mechanisms leading to increases or decreases in enzyme activities as the concept of enzyme induction via nuclear receptors and the different mechanisms of enzyme inhibition are explained. With these basics in mind, various influencing factors are discussed, including physiological and pathological conditions, as well as drugs, nutrients and environmental agents with a special focus on drug-drug interactions.
With a foreword by Prof Leslie Z. Benet, the world's best and best-known biopharmaceutical scientist.
Bibliographische Angaben
- Autoren: Bernard Testa , Stefanie D. Krämer
- 2010, 700 Seiten, Maße: 17,4 x 24,7 cm, Gebunden, Englisch
- Verlag: Wiley-VCH
- ISBN-10: 3906390551
- ISBN-13: 9783906390550
- Erscheinungsdatum: 12.05.2010
Sprache:
Englisch
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