Thursday, 19 September 2013

Drug Metabolism: Chemical and Enzymatic Aspects

Drugs and other xenobiotics can exert a wide variety of pharmacological and toxic effects. In order to understand these effects it is necessary to understand both the structural parameters that are a direct cause of these effects as well as the factors that control the concentration of the drug in the body, such as absorption, metabolism, and elimination. To fully appreciate drug action requires at least minimal expertise in a variety of disciplines such as chemistry, biochemistry, kinetics and biology. While complicated and demanding in its breadth such knowledge is central to the knowledge base of advanced students of Pharmacy, Pharmacokinetics, Medicinal Chemistry, Pharmacology and Toxicology. However, texts that focus on covering these disciplines in rationalizing drug action are rare. Furthermore, many of the effects are due to metabolites rather than due to the parent drug/xenobiotic and some metabolites, or intermediates that lead to metabolites, are chemically reactive. Therefore, when considering the effects of an agent, all of the metabolites that the body produces from the agent must also be taken into consideration. To try and address the gap in multidisciplinary knowledge required, as the title suggests, the focus of this book is on the chemistry, enzymology and to a lesser extent the kinetics of drug metabolism. As indicated above an understanding of this subject at a minimum requires a basic understanding of the chemistry involved. It is also important that these processes be placed into a biological context. Therefore, Chapter 2 entitled "Background for Nonchemists" and Chapter 3 entitled "Background for Chemists" attempt to explicitly confront these issues and provide the necessary background and context. Since chemically reactive metabolites have major implications for toxicity and since understanding their generation and properties requires the spectrum of disciplines outlined above a chapter is devoted to reactive metabolites. Finally, the only way to master the subject is with practice. Sample problems with answers are provided to facilitate this process.



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