This introduction to the mechanisms by which the body metabolizes and excretes administered drugs is directed at advanced undergraduate biochemists, pharmacologists, pre-clinical medical strudents and advanced undergraduate/postgraduate toxicologists. The subject is approached from both biochemical and physiological angles. The examples of drug metabolism have been kept clinically relevant, so that the practical importance of the subject can be easily appreciated. The book contains a section of experimental procedures for setting up student practicals in drug metabolism.
This introduction to the mechanisms by which the body metabolizes and excretes administered drugs is directed at advanced undergraduate biochemists, pharmacologists, pre-clinical medical strudents and advanced undergraduate/postgraduate toxicologists. The subject is approached from both biochemical and physiological angles. The examples of drug metabolism have been kept clinically relevant, so that the practical importance of the subject can be easily appreciated. The book contains a section of experimental procedures for setting up student practicals in drug metabolism.
Part 1 Pathways of drug metabolism: phase I metabolism - oxidations involving the microsomal mixed-function oxidase (cytochrome P450), oxidation other than the microsomal mixed-function oxidase, reductive metabolism, hydrolysis, hydration, other phase I reactions, summary of phase I metabolism; phase II metabolism - conjugation with sugars, sulfation, methylation, acetylation, amino acid conjugation, glutathione conjugation, fatty acid and cholesteryl ester conjugation, condensation reactions, stereoselective reactions, summary of phase II metabolism; summary; endogenous metabolism related to drug metabolism - phase I, phase II; general summary. Part 2 Enzymology and molecular mechanisms of drug metabolism reactions: cytochrome P450-dependent mixed function oxidation reactions - components of the MFO system, catalytic cycle of cytochrome P450; microsomal flavin-containing monoxygenase; prostaglandin synthetase-dependent co-oxidation of drugs; reductive drug metabolism; epoxide hydrolase; glucuronide conjugation reactions; glutathione-S-transferase; sulfate conjugation; amino acid conjugation; control and interactions of drug metabolism pathways - substrate and oxygen availability, NADPH supply, synthesis and degradation of cytochrome P450, control of drug metabolism by endogenous co-substrates, participation of cytochrome b5, glucuronidation, cellular competition for glutathione. Part 3 Induction and inhibition of drug metabolism: induction of drug metabolism - induction of drug metabolism in man, induction of drug metabolism in experimental animals, role of cytochrome P450 in the induction of drug metabolism, induction of multiple forms (isoenzymes) of cytochrome P450, significance of multiple forms of cytochrome P450, induction of extrahepatic drug metabolism, mechanisms of cytochrome P450 induction, induction of non-cytochrome P450 drug metabolizing enzymes; inhibition of drug metabolism - inhibition of drug metabolism by destruction of hepatic cytochrome P450, metal ions and hepatic cytochrome P450, inhibition of drug metabolism by compounds forming inactive complexes with hepatic cytochrome P450, inhibition of drug metabolism - miscellaneous drugs and xenobiotics; conclusions. (Part contents).
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