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.
Thursday, 19 September 2013
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